Affinage

Showing PTGDR2 — CRTH2 is a alias.

PTGDR2

Prostaglandin D2 receptor 2 · UniProt Q9Y5Y4

Length
395 aa
Mass
43.3 kDa
Annotated
2026-06-10
100 papers in source corpus 33 papers cited in narrative 33 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PTGDR2 (CRTH2/GPR44/DP2) is a seven-transmembrane G protein-coupled receptor for prostaglandin D2 (PGD2) that drives chemotaxis and activation of Th2 cells, eosinophils, and basophils, functioning as a central effector of type 2 immune and allergic inflammation (PMID:11208866). The receptor binds PGD2 with high affinity and signals predominantly through pertussis toxin-sensitive Gαi/o, lowering cAMP and mobilizing intracellular Ca2+ (PMID:12466225), while its ligand pocket is also engaged by indomethacin and stable thromboxane/PGD2 metabolites such as 11-dehydro-thromboxane B2 and 9α,11β-PGF2, with mutagenesis and crystallographic analysis defining a semi-occluded, charge-attraction ligand entry site whose determinants for PGD2 and indomethacin are overlapping but distinct (PMID:11801628, PMID:14668348, PMID:16030019, PMID:30220562). Downstream of Gαi, CRTH2 engages PI3K-dependent chemotaxis and actin polymerization together with Ca2+/calcineurin/NFAT-driven cytokine production, and a PI3K/Akt arm that protects Th2 cells from cytokine-deprivation apoptosis (PMID:17196174, PMID:19494281); signaling is also dissectible into G protein-dependent and β-arrestin-dependent pathways, with GRK2/5/6- and PKA-mediated phosphorylation driving β-arrestin-dependent internalization and Rab11-dependent recycling (PMID:15870392, PMID:17207480). In vivo, CRTH2 mediates PGD2-induced eosinophil airway trafficking and ILC2 accumulation in inflamed lung, and its loss attenuates allergic skin inflammation, viral (COX-2/PGD2-driven) asthma exacerbation, Th2-dependent renal and pulmonary vascular remodeling, and sepsis pathology (PMID:16888024, PMID:15528449, PMID:18097056, PMID:25850654, PMID:29970474, PMID:22544936, PMID:22997255). Beyond classical Gαi immune signaling, CRTH2 couples to Gαq in cardiomyocytes to activate an m-calpain/caspase-12 cascade promoting ER stress-induced apoptosis after myocardial infarction (PMID:29335338), and in fibroblasts is trafficked to the ER membrane where its N-terminus binds LARP6 to destabilize collagen mRNA and limit fibrosis (PMID:34223653). CRTH2 additionally restrains gastric cancer stem cell self-renewal by inhibiting STAT3 phosphorylation, controls peripheral nerve myelination through Schwann-cell Nfatc4, and shapes intestinal epithelial type 2 responses by downregulating Il13ra1 (PMID:29604141, PMID:25362470, PMID:34283207).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 2001 High

    Established that CRTH2 is a functional PGD2 receptor coupling type 2 immune effector cells to chemotaxis and Ca2+ signaling, defining its core biological role.

    Evidence CRTH2 transfection with Ca2+ mobilization and chemotaxis assays plus pertussis toxin inhibition in Th2 cells, eosinophils, basophils; selective agonist DK-PGD2 in primary eosinophils

    PMID:11208866 PMID:11742277

    Open questions at the time
    • Did not resolve the receptor pharmacology versus the DP receptor
    • Downstream effectors beyond Ca2+ not yet mapped
  2. 2002 High

    Defined CRTH2 ligand-binding pharmacology and Gαi/o coupling, and revealed that indomethacin is a direct agonist independent of COX inhibition, distinguishing CRTH2 from the DP receptor.

    Evidence Radioligand saturation/competition binding, cAMP and Ca2+ assays with pertussis toxin and anti-CRTH2 mAb in recombinant and primary cells

    PMID:11801628 PMID:12466225

    Open questions at the time
    • Structural basis of distinct PGD2 versus indomethacin recognition not yet known
    • G protein-independent signaling not addressed
  3. 2003 High

    Expanded the endogenous ligand repertoire and confirmed conserved Gαi/PI3K-dependent chemotaxis in the mouse receptor, with phospholipase C implicated in signaling.

    Evidence Transfected-cell chemotaxis and Ca2+ flux with selective inhibitors (ramatroban, U73122, wortmannin, PTX); mouse CRTH2 radioligand binding and cAMP assays

    PMID:12721327 PMID:14668348

    Open questions at the time
    • Physiological relevance of TXA2/PGD2 metabolites as ligands unresolved
    • Conditions favoring PLC versus Gαi coupling not defined
  4. 2005 High

    Mapped the ligand-binding pocket and demonstrated that CRTH2 G protein-dependent and β-arrestin-dependent pathways are pharmacologically separable, establishing biased signaling.

    Evidence Site-directed mutagenesis with binding and functional assays; GTPγS and β-arrestin translocation assays with allosteric indole compounds; further endogenous agonists and PLC/Gq pharmacology

    PMID:15870392 PMID:16030019 PMID:16256979 PMID:16378605

    Open questions at the time
    • Physiological output of β-arrestin pathway not defined
    • Gq coupling shown pharmacologically but not at a defined effector
  5. 2006 High

    Resolved the downstream signaling architecture (PI3K-chemotaxis, calcineurin/NFAT-cytokine) and the trafficking machinery (GRK2/5/6, PKA, β-arrestin, Rab11), distinguishing CRTH2 regulation from the DP receptor.

    Evidence Pathway inhibitors and functional readouts in primary Th2 cells; GRK/PKC/PKA and Rab co-expression with immunofluorescence in HEK293; CRTH2-knockout contact hypersensitivity model

    PMID:16888024 PMID:17196174 PMID:17207480

    Open questions at the time
    • Specific GRK phosphorylation sites not identified
    • Whether biased signaling alters in vivo inflammation untested
  6. 2009 High

    Showed CRTH2 PI3K/Akt signaling is pro-survival in Th2 cells, extending its role from migration to lymphocyte persistence.

    Evidence LY294002 inhibition, annexin V apoptosis assays, and Western blots for pAkt/pBAD/cytochrome c/caspase-3 in primary human Th2 cells

    PMID:19494281

    Open questions at the time
    • Anti-apoptotic role specific to cytokine deprivation; not generalizable to Fas-mediated death
    • In vivo contribution to Th2 cell longevity untested
  7. 2012 High

    Established CRTH2 as a regulator beyond Th2 immunity: it restrains neutrophil responses in sepsis via epigenetic CXCR2 control and drives Th2-dependent renal fibrosis, broadening its pathophysiological reach.

    Evidence CRTH2-knockout mice in CLP sepsis with ChIP at the CXCR2 promoter and neutrophil/CXCR2 epistasis; L-PGDS and CRTH2 knockouts in UUO fibrosis with IL-4/IL-13 ablation; beta-cell radioligand imaging

    PMID:22544936 PMID:22997255 PMID:26467464

    Open questions at the time
    • Mechanism linking CRTH2 signaling to histone H3 acetylation undefined
    • Cell-type origin of fibrosis-driving Th2 response not fully resolved
  8. 2015 Medium

    Identified CRTH2 as cell-intrinsically required for ILC2 lung migration and as a mediator of PGD2-dependent suppression of hair follicle neogenesis and of depression-related behavior, revealing roles outside adaptive immunity.

    Evidence CRTH2-knockout mice with ILC2 adoptive-transfer rescue in helminth infection; Gpr44-null WIHN model with exogenous PGD2; knockout and ramatroban depression models with monoamine analysis

    PMID:23190891 PMID:25698598 PMID:25850654

    Open questions at the time
    • Neuronal CRTH2 site of action in depression not localized
    • Hair follicle and behavioral mechanisms only partially defined
  9. 2018 High

    Crystal structures and discovery of Gαq-coupled cardiomyocyte apoptosis and STAT3-dependent tumor suppression redefined CRTH2 as a structurally tractable receptor with context-dependent G protein coupling and non-immune functions.

    Evidence X-ray crystallography with antagonists and docking; CRTH2-knockout MI/doxorubicin models with m-calpain/caspase-12 dissection; PTGDR2 knockdown/PGD2 stimulation with STAT3 Thr705 mutagenesis and tumor models; beta-cell PET imaging; PAH knockout/adoptive transfer studies

    PMID:29208633 PMID:29335338 PMID:29604141 PMID:29970474 PMID:30220562

    Open questions at the time
    • Structural determinants of Gαi versus Gαq coupling not resolved
    • Tissue determinants of agonist versus suppressive output undefined
  10. 2021 High

    Revealed a non-canonical intracellular function in which ER-trafficked CRTH2 binds LARP6 to suppress collagen mRNA, and a non-hematopoietic epithelial role downregulating Il13ra1, separating CRTH2 biology from its plasma-membrane GPCR signaling.

    Evidence Subcellular fractionation, CRTH2-LARP6 Co-IP, caveolin-1 knockdown, CRTH2/LARP6 knockout fibrosis models with N-terminal peptide rescue; CRTH2 conditional knockout and organoids in intestinal type 2 responses

    PMID:34223653 PMID:34283207

    Open questions at the time
    • How a 7TM GPCR is routed to the ER membrane and oriented to bind LARP6 not fully explained
    • Relationship between intracellular and surface CRTH2 pools in fibroblasts unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural and cellular rules governing CRTH2's switch between Gαi-driven chemotactic signaling, Gαq-driven apoptotic signaling, β-arrestin-biased pathways, and ligand-independent intracellular LARP6 scaffolding remain unresolved.
  • No unified model for tissue-specific G protein coupling selection
  • Trafficking determinants of surface versus ER versus intracellular CRTH2 not defined
  • Whether biased ligands can selectively engage immune versus non-immune functions untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 4 GO:0060089 molecular transducer activity 3 GO:0008289 lipid binding 2 GO:0003723 RNA binding 1
Localization
GO:0005886 plasma membrane 3 GO:0005768 endosome 1 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-168256 Immune System 4 R-HSA-162582 Signal Transduction 3 R-HSA-5357801 Programmed Cell Death 2 R-HSA-8953854 Metabolism of RNA 1
Partners
ARRBCAV1GRK2GRK5GRK6LARP6RAB11

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 CRTH2 is a functional receptor for prostaglandin D2 (PGD2) that induces intracellular Ca2+ mobilization and chemotaxis in Th2 cells, eosinophils, and basophils in a Gαi-dependent (pertussis toxin-sensitive) manner. Transfection of CRTH2 in cell lines, Ca2+ mobilization assay, chemotaxis assay, pertussis toxin inhibition The Journal of experimental medicine High 11208866
2002 Recombinant human CRTH2 binds PGD2 with high and low affinity sites (Kd 2.5 and 109 nM); ligand rank order differs markedly from DP receptor; PGD2 activation decreases intracellular cAMP in a pertussis toxin-sensitive manner, confirming functional coupling to Gαi/o. Radioligand binding (saturation and competition), cAMP assay, pertussis toxin treatment in HEK293(EBNA) cells expressing recombinant hCRTH2 British journal of pharmacology High 12466225
2002 Indomethacin acts as a direct agonist of CRTH2 (not via COX inhibition or PPARs), inducing Ca2+ mobilization and chemotaxis of Th2 cells, eosinophils, and basophils at submicromolar concentrations via Gαi-dependent signaling; effects are blocked by anti-CRTH2 mAb. Ca2+ mobilization assay in CRTH2-transfected K562 cells, chemotaxis assay with CRTH2+ primary cells, anti-CRTH2 mAb blocking, comparison with other NSAIDs Journal of immunology High 11801628
2001 CRTH2 mediates PGD2-induced eosinophil chemokinesis, degranulation, and morphology changes; selective CRTH2 agonist DK-PGD2 (but not DP agonist BW245C) reproduces these effects; DP (not CRTH2) mediates eosinophil survival/anti-apoptotic effects. Human eosinophil isolation, chemokinesis assay, degranulation assay, selective agonists DK-PGD2 and BW245C The Journal of allergy and clinical immunology High 11742277
2003 11-Dehydro-thromboxane B2 (a stable TXA2 metabolite) is a full agonist of CRTH2, inducing Ca2+ flux from intracellular stores in eosinophils and chemotaxis in CRTH2-transfected BaF/3 cells; responses are blocked by CRTH2/TP antagonist ramatroban but not by selective TP antagonist SQ29548; PLC inhibitor U73,122 attenuated both 11-dehydro-TXB2- and PGD2-induced shape change, implicating phospholipase C in CRTH2 signaling. Flow cytometric shape change assay, Ca2+ flux assay, chemotaxis with CRTH2-transfected BaF/3 cells, selective pharmacological inhibitors, cross-desensitization experiments The Journal of biological chemistry High 14668348
2003 Mouse CRTH2 binds PGD2 with high affinity (Kd ~8.8 nM), inhibits cAMP generation via pertussis toxin-sensitive Gi, and mediates chemotaxis through PI3-kinase signaling; indomethacin also binds and activates mCRTH2 with micromolar affinity. Saturation radioligand binding, cAMP assay, chemotaxis assay with wortmannin (PI3K inhibitor) and PTX in HEK293 cells expressing mouse CRTH2 The Journal of pharmacology and experimental therapeutics High 12721327
2005 Site-directed mutagenesis of CRTH2 identified specific transmembrane residues (His-106/TM III, Lys-209/TM V, Glu-268/TM VI) and extracellular loop II residue Arg-178 as critical for PGD2 binding; H106A and E268A mutants retained indomethacin binding, demonstrating overlapping but distinct binding determinants; Glu-268 contributes to prostanoid selectivity; Tyr-261 is required for indomethacin but not PGD2 binding. Site-directed mutagenesis, radioligand competition binding, cAMP functional assay, chemotaxis assay in HEK293 cells The Journal of biological chemistry High 16030019
2005 Two indole derivatives that occupy CRTH2 simultaneously with PGD2 selectively inhibit PGD2-mediated β-arrestin translocation (G protein-independent pathway) without affecting Gαi activation, demonstrating that CRTH2 has distinct G protein-dependent and G protein-independent signaling pathways that can be pharmacologically dissociated. Whole-cell saturation binding, ELISA for surface receptor levels, GTPγS binding assay, β-arrestin translocation assay, eosinophil shape change assay Molecular pharmacology High 15870392
2006 CRTH2-mediated responses in Th2 cells involve PI3K and Ca2+/calcineurin/NFAT signaling: PI3K inhibition (LY294002) reduces both PGD2-induced chemotaxis and cytokine production (IL-4, IL-5, IL-13) and actin polymerization; calcineurin inhibitors (FK506, cyclosporin A) block cytokine production and NFATc1 nuclear translocation but not chemotaxis; GSK3β negatively regulated by PI3K contributes to NFAT nuclear localization. Signaling pathway inhibitors (LY294002, FK506, cyclosporin A, SB216763) on primary human CRTH2+ CD4+ Th2 cells; chemotaxis, cytokine ELISA, actin polymerization, and NFAT nuclear translocation assays Biochemical pharmacology High 17196174
2006 CRTH2 internalization requires GRK2, GRK5, or GRK6 (whereas DP only requires GRK2); CRTH2 undergoes basal phosphorylation by PKA contributing to its internalization; PKC and PKA inhibition reduces PGD2-induced CRTH2 internalization; CRTH2 recycling involves Rab11 (distinct from DP which uses Rab4), indicating differential post-endocytic trafficking of the two PGD2 receptors. Co-expression of GRKs, PKC/PKA pharmacological inhibition, Rab GTPase co-expression, arrestin co-expression, immunofluorescence microscopy in HEK293 cells European journal of pharmacology High 17207480
2009 CRTH2 activation by PGD2 in Th2 cells protects against cytokine deprivation-induced apoptosis via PI3K/Akt pathway: PGD2 induces Akt and BAD phosphorylation, prevents cytochrome c release from mitochondria, and suppresses caspase-3 and PARP cleavage; this anti-apoptotic effect is blocked by PI3K inhibitor LY294002 and is specific to cytokine deprivation-induced (not Fas-mediated) apoptosis. PI3K inhibition (LY294002), annexin V/PI apoptosis assay, Western blotting for pAkt, pBAD, cytochrome c, caspase-3, PARP; selective CRTH2 agonist/antagonist pharmacology in primary human Th2 cells Journal of immunology High 19494281
2006 CRTH2-deficient mice show significantly reduced chronic allergic skin inflammation (contact hypersensitivity), with 35-55% reduction in ear-swelling, decreased infiltration of lymphocytes, eosinophils, and basophils, and reduced production of MDC and RANTES. Genetic or pharmacological CRTH2 blockade also reduced serum IgE production in chronic CHS model but did not impair Langerhans cell/DC migration to lymph nodes. CRTH2 gene-targeted knockout mice, hematopoietic PGD synthase inhibitor (HQL-79), CRTH2 antagonist ramatroban, IgE ELISA, histology, chemokine quantification Journal of immunology High 16888024
2018 Crystal structures of human CRTH2 with antagonists fevipiprant and CAY10471 reveal a semi-occluded ligand-binding pocket covered by a structured amino terminus; structural analysis suggests a ligand entry port with charge-attraction facilitating PGD2 binding distinct from the binding mechanisms of lysophospholipids and endocannabinoids. X-ray crystallography, docking, ligand-binding competition assays Molecular cell High 30220562
2018 CRTH2 is expressed in cardiomyocytes and couples to Gαq to elicit intracellular Ca2+ flux, activating the m-calpain/caspase-12 cascade to promote ER stress-induced cardiomyocyte apoptosis; CRTH2 disruption improves cardiac recovery post-myocardial infarction; knockdown of caspase-4 (human ortholog of caspase-12) attenuates CRTH2 activation-induced apoptosis in human cardiomyocytes. CRTH2 knockout mice (MI and doxorubicin models), siRNA knockdown, Ca2+ flux assay, m-calpain activity assay, caspase-12/4 activity measurement, Western blotting EMBO molecular medicine High 29335338
2021 In fibroblasts, CRTH2 is trafficked from the plasma membrane to the ER membrane in a caveolin-1-dependent manner; ER-anchored CRTH2 binds the collagen mRNA recognition motif of LARP6 and promotes degradation of collagen mRNA, thereby antagonizing collagen biosynthesis; CRTH2 deficiency increases collagen production and exacerbates organ fibrosis in mice, which is rescued by LARP6 depletion. CRTH2 N-terminal peptide reproduces this anti-fibrotic effect. Subcellular fractionation, co-immunoprecipitation (CRTH2-LARP6 interaction), caveolin-1 knockdown, CRTH2/LARP6 knockout mice (bleomycin lung fibrosis and UUO kidney fibrosis models), collagen mRNA stability assay, CRTH2 N-terminal peptide administration The EMBO journal High 34223653
2018 PGD2/PTGDR2 signaling restricts gastric cancer stem cell self-renewal by inhibiting STAT3 phosphorylation (Thr705) and nuclear expression; knockdown of PTGDR2 enhances cancer stem cell markers and self-renewal, while PGD2 stimulation suppresses them; mutation of STAT3 Thr705 abrogates the inhibitory effect of PGD2. PTGDR2 knockdown, PGD2 stimulation, STAT3 phosphorylation Western blot, nuclear fractionation, tumor sphere assay, subcutaneous and peritoneal metastasis mouse models, STAT3 phosphorylation site mutagenesis Stem cells High 29604141
2014 In peripheral nervous system myelination, neuronally secreted PGD2 signals through glial Gpr44 (CRTH2/PTGDR2); in vivo ablation and in vitro knockdown of glial Gpr44 impairs myelination; Nfatc4, a transcription factor for myelination, is identified as a downstream effector of PGD2/Gpr44 signaling in Schwann cells. Gpr44 in vivo ablation (knockout mice), in vitro Gpr44 knockdown in Schwann cells, myelination assays, Nfatc4 identification as downstream target Nature neuroscience High 25362470
2012 CRTH2 is expressed on GPR44+ pancreatic beta cells and can be targeted for in vivo visualization of beta cells; radiolabeled GPR44 antagonist [3H]AZD 3825 shows ~50-fold higher specific binding to beta cells vs. exocrine pancreas. Radioligand binding assay ([3H]AZD 3825), flow cytometry for surface expression, in vitro autoradiography Acta diabetologica Medium 26467464
2017 Radiolabeled CRTH2/GPR44 antagonist [11C]AZ12204657 binds specifically to GPR44 in pancreas and spleen in vivo; binding is competed away dose-dependently in nondiabetic animals but not in diabetic animals, suggesting GPR44 expression is linked to functional beta cell mass. PET imaging with [11C]AZ12204657 in pigs and nonhuman primates, immunodeficient mouse transplantation model with human islets, in vitro autoradiography Diabetes Medium 29208633
2004 Human osteoblasts express CRTH2; selective CRTH2 activation increases intracellular calcium (while DP increases cAMP), decreases RANKL expression, and induces osteoblast chemotaxis, suggesting an anabolic role in bone. RT-PCR, immunohistochemistry, intracellular cAMP/Ca2+ assays, RANKL ELISA, chemotaxis assay in primary human osteoblasts with selective agonists DK-PGD2 (CRTH2) and BW245C (DP) Journal of bone and mineral research Medium 15765187
2004 CRTH2 mediates in vivo PGD2-induced eosinophil trafficking into the airways: intratracheal CRTH2-specific agonists (but not DP or TP agonists) induce airway eosinophilia in IL-5-primed rats; a CRTH2/TP antagonist nearly completely blocks this response while TP- or DP-specific antagonists do not. Intratracheal instillation of selective agonists/antagonists in IL-5-pretreated rats, BAL cell counts, lung histology The Journal of pharmacology and experimental therapeutics High 15528449
2005 9α,11β-PGF2 (a major in vivo allergen challenge metabolite) and its stereoisomer PGF2α are novel agonists of CRTH2, capable of inducing cell migration and activation, expanding the repertoire of endogenous CRTH2 ligands beyond PGD2 and its direct metabolites. CRTH2 agonist cell migration and activation assays with PGD2 metabolite panel FEBS letters Medium 16378605
2008 dsRNA (mimicking viral infection) enhances allergic airway inflammation via COX-2-dependent PGD2 synthesis in alveolar macrophages followed by CRTH2-mediated eosinophil recruitment; CRTH2-deficient mice do not exhibit dsRNA-induced increase in eosinophil accumulation, placing CRTH2 downstream of COX-2/PGD2 in viral exacerbation of asthma. Intratracheal poly I:C instillation, COX-2 immunostaining, PGD2 measurement, CRTH2-deficient mice, dual CRTH2/TP antagonist vs. TP-specific antagonist Journal of immunology High 18097056
2015 CRTH2 regulates in vivo accumulation of ILC2s in the lung: murine ILC2s express CRTH2, migrate toward PGD2 in vitro, and accumulate in the lung in response to PGD2 in vivo; CRTH2-deficient mice show reduced ILC2 responses in helminth-induced pulmonary inflammation; adoptive transfer of CRTH2-sufficient (but not CRTH2-deficient) ILC2s restores pulmonary inflammation in CRTH2-deficient hosts. CRTH2-knockout mice, in vitro migration assay, intranasal PGD2 administration, Nippostrongylus brasiliensis infection model, adoptive transfer of CRTH2+/+ vs CRTH2-/- ILC2s Mucosal immunology High 25850654
2020 CRTH2 expression on ILC2s is required for IL-33-driven ILC2 accumulation in the lung; this effect is not due to differences in proliferation, apoptosis, or ST2 expression; adoptive transfer experiments show CRTH2-deficient ILC2s have altered migration patterns and fail to preferentially accumulate in inflamed lung tissue compared to wild-type ILC2s. CRTH2-knockout mice, systemic IL-33 treatment, adoptive transfer of CRTH2+/+ vs CRTH2-/- ILC2s, flow cytometric analysis of proliferation (Ki-67), apoptosis, ST2 expression Journal of immunology High 31900341
2021 CRTH2 expressed on non-hematopoietic intestinal epithelial cells (including stem, goblet, and tuft cells) negatively regulates Type 2 cytokine-driven epithelial responses; CRTH2-deficient mice and organoids show enhanced goblet cell differentiation and worm clearance; PGD2/CRTH2 signaling downregulates epithelial Il13ra1 expression and reverses IL-13-mediated suppression of cell proliferation. CRTH2 conditional knockout (non-hematopoietic cells), intestinal organoid culture, CRTH2-/- mice infected with Nippostrongylus brasiliensis, Il13ra1 expression analysis, goblet cell quantification The Journal of experimental medicine High 34283207
2018 CRTH2 expression is upregulated on circulating CD4+ T cells in idiopathic PAH patients and rodent models; CRTH2 disruption ameliorates pulmonary arterial remodeling and hypertension; CRTH2 deficiency suppresses Th2 activation (IL-4, IL-13 secretion); CRTH2+ bone marrow reconstitution and CD4+ T cell adoptive transfer worsen PAH in CRTH2-/- mice, reversed by dual IL-4/IL-13 neutralization; CRTH2 activation in Th2 cells promotes PASMC proliferation via STAT6. CRTH2-knockout mice, bone marrow reconstitution, adoptive transfer of CRTH2+/+ CD4+ T cells, IL-4/IL-13 dual neutralization, PASMC proliferation assay, STAT6 phosphorylation analysis The Journal of experimental medicine High 29970474
2012 CRTH2 deficiency improves neutrophil migration and survival in polymicrobial sepsis (CLP model); CRTH2-/- mice have higher CXCR2 expression on neutrophils, greater peritoneal bacterial clearance, and elevated IL-10; CLP reduces acetylation of histone H3 at the CXCR2 promoter in wild-type neutrophils, suggesting epigenetic regulation of CXCR2 by CRTH2 signaling; neutrophil depletion or CXCR2 inhibition abrogates the survival benefit in CRTH2-/- mice. CRTH2-knockout mice, CLP sepsis model, flow cytometric CXCR2 analysis, ChIP for histone H3 acetylation at CXCR2 promoter, neutrophil depletion, CXCR2 antagonism Journal of immunology High 22544936
2012 PGD2/CRTH2 pathway promotes renal tubulointerstitial fibrosis via CRTH2-mediated Th2 lymphocyte activation; L-PGDS and CRTH2 knockout mice both show reduced renal fibrosis, reduced Th2 infiltration, and decreased IL-4 and IL-13 after UUO; ablation of IL-4 and IL-13 also ameliorates fibrosis, placing Th2 cytokines downstream of CRTH2. L-PGDS and CRTH2 knockout mice, UUO model, oral CRTH2 antagonist, IL-4/IL-13 measurement, histological fibrosis scoring Journal of the American Society of Nephrology High 22997255
2015 CRTH2/Gpr44 mediates PGD2-induced inhibition of wound-induced hair follicle neogenesis (WIHN): Gpr44-null mice show increased WIHN and are resistant to exogenous PGD2-induced inhibition of follicle neogenesis. Gpr44-knockout mice, exogenous PGD2 application, WIHN quantification, Ptgds expression and PGD2 level correlation across mouse strains The Journal of investigative dermatology High 23190891
2015 CRTH2 mediates depression-related behavior: CRTH2-deficient mice show antidepressant-like activity in chronic corticosterone-induced depression; pharmacological CRTH2 inhibition with ramatroban rescues depression-related behavior in corticosterone-, LPS-, and tumor-induced depression models; CRTH2 ablation is associated with increased hippocampal noradrenergic (but not dopaminergic or serotonergic) activity. CRTH2-knockout mice, chronic corticosterone/LPS/tumor depression models, ramatroban pharmacological treatment, forced swim test, social interaction test, monoamine system analysis Behavioural brain research Medium 25698598
2005 CRTH2-mediated eosinophil responses involve phospholipase C activation as demonstrated by the inhibitory effect of U73,122; activation is pertussis toxin-insensitive for shape change responses to 11-dehydro-TXB2, suggesting coupling to a Gq-type protein in addition to Gi in certain contexts. PLC inhibitor U73,122, pertussis toxin treatment, eosinophil shape change assay, Ca2+ flux European journal of pharmacology Medium 16256979
2014 Human mast cells express DP2/CRTH2 intracellularly rather than on the cell surface; intracellular CRTH2 activation by selective agonists induces pertussis toxin-sensitive Ca2+ mobilization but does not induce degranulation, contrasting with surface-expressed CRTH2 on other immune cells. Imaging flow cytometry for surface vs. intracellular DP2, aspirin blockade experiment, PTX treatment, Ca2+ mobilization assay, degranulation assay in human MC lines and primary cultured MC PloS one Medium 25268140

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 Human IL-25- and IL-33-responsive type 2 innate lymphoid cells are defined by expression of CRTH2 and CD161. Nature immunology 972 21909091
2001 Prostaglandin D2 selectively induces chemotaxis in T helper type 2 cells, eosinophils, and basophils via seven-transmembrane receptor CRTH2. The Journal of experimental medicine 882 11208866
2000 CRTH2 is the most reliable marker for the detection of circulating human type 2 Th and type 2 T cytotoxic cells in health and disease. European journal of immunology 249 11069080
1999 CRTH2, an orphan receptor of T-helper-2-cells, is expressed on basophils and eosinophils and responds to mast cell-derived factor(s). FEBS letters 249 10518017
2001 Selective modulation of chemokinesis, degranulation, and apoptosis in eosinophils through the PGD2 receptors CRTH2 and DP. The Journal of allergy and clinical immunology 200 11742277
2015 The prostaglandin D₂ receptor CRTH2 regulates accumulation of group 2 innate lymphoid cells in the inflamed lung. Mucosal immunology 193 25850654
2011 A randomized, double-blind, placebo-controlled study of the CRTH2 antagonist OC000459 in moderate persistent asthma. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 177 21762224
2005 Activation of the prostaglandin D2 receptor DP2/CRTH2 increases allergic inflammation in mouse. Journal of immunology (Baltimore, Md. : 1950) 174 15749909
2013 Anti-eosinophil activity and clinical efficacy of the CRTH2 antagonist OC000459 in eosinophilic esophagitis. Allergy 173 23379537
2006 Emerging roles of DP and CRTH2 in allergic inflammation. Trends in molecular medicine 169 16545607
2002 Molecular pharmacology of the human prostaglandin D2 receptor, CRTH2. British journal of pharmacology 169 12466225
2006 Prostaglandin D2 plays an essential role in chronic allergic inflammation of the skin via CRTH2 receptor. Journal of immunology (Baltimore, Md. : 1950) 158 16888024
2007 The roles of the prostaglandin D(2) receptors DP(1) and CRTH2 in promoting allergic responses. British journal of pharmacology 134 17965752
2002 Cutting edge: agonistic effect of indomethacin on a prostaglandin D2 receptor, CRTH2. Journal of immunology (Baltimore, Md. : 1950) 124 11801628
2003 The second PGD(2) receptor CRTH2: structure, properties, and functions in leukocytes. Prostaglandins, leukotrienes, and essential fatty acids 118 12895600
2007 Antagonism of the prostaglandin D2 receptor CRTH2 attenuates asthma pathology in mouse eosinophilic airway inflammation. Respiratory research 106 17328802
2017 Targeting the PGD2/CRTH2/DP1 Signaling Pathway in Asthma and Allergic Disease: Current Status and Future Perspectives. Drugs 105 28612233
2019 KLRG1 and NKp46 discriminate subpopulations of human CD117+CRTH2- ILCs biased toward ILC2 or ILC3. The Journal of experimental medicine 104 31201208
2010 CRTH2 and D-type prostanoid receptor antagonists as novel therapeutic agents for inflammatory diseases. Pharmacology 95 20559016
2004 Prostaglandin D2-induced eosinophilic airway inflammation is mediated by CRTH2 receptor. The Journal of pharmacology and experimental therapeutics 93 15528449
2016 The oral CRTh2 antagonist QAW039 (fevipiprant): A phase II study in uncontrolled allergic asthma. Pulmonary pharmacology & therapeutics 86 27354118
2017 Fevipiprant, an oral prostaglandin DP2 receptor (CRTh2) antagonist, in allergic asthma uncontrolled on low-dose inhaled corticosteroids. The European respiratory journal 85 28838980
2003 11-Dehydro-thromboxane B2, a stable thromboxane metabolite, is a full agonist of chemoattractant receptor-homologous molecule expressed on TH2 cells (CRTH2) in human eosinophils and basophils. The Journal of biological chemistry 84 14668348
2004 Sequence variants of the gene encoding chemoattractant receptor expressed on Th2 cells (CRTH2) are associated with asthma and differentially influence mRNA stability. Human molecular genetics 82 15345705
2018 PGD2/PTGDR2 Signaling Restricts the Self-Renewal and Tumorigenesis of Gastric Cancer. Stem cells (Dayton, Ohio) 76 29604141
2014 Setipiprant, a selective CRTH2 antagonist, reduces allergen-induced airway responses in allergic asthmatics. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 75 24964348
2005 Identification of indole derivatives exclusively interfering with a G protein-independent signaling pathway of the prostaglandin D2 receptor CRTH2. Molecular pharmacology 75 15870392
2012 Prostaglandin D2 inhibits wound-induced hair follicle neogenesis through the receptor, Gpr44. The Journal of investigative dermatology 72 23190891
2018 CRTH2 promotes endoplasmic reticulum stress-induced cardiomyocyte apoptosis through m-calpain. EMBO molecular medicine 70 29335338
2008 Cyclooxygenase-2/prostaglandin D2/CRTH2 pathway mediates double-stranded RNA-induced enhancement of allergic airway inflammation. Journal of immunology (Baltimore, Md. : 1950) 70 18097056
2004 Expression of prostaglandin D synthase and the prostaglandin D2 receptors DP and CRTH2 in human nasal mucosa. Prostaglandins & other lipid mediators 68 15165034
2014 Prostaglandin D2 synthase/GPR44: a signaling axis in PNS myelination. Nature neuroscience 65 25362470
1999 Molecular cloning, chromosome mapping and characterization of the mouse CRTH2 gene, a putative member of the leukocyte chemoattractant receptor family. Gene 65 9931443
2018 Structures of the Human PGD2 Receptor CRTH2 Reveal Novel Mechanisms for Ligand Recognition. Molecular cell 63 30220562
2009 Novel function of CRTH2 in preventing apoptosis of human Th2 cells through activation of the phosphatidylinositol 3-kinase pathway. Journal of immunology (Baltimore, Md. : 1950) 63 19494281
2004 Production of prostaglandin D(2) by human osteoblasts and modulation of osteoprotegerin, RANKL, and cellular migration by DP and CRTH2 receptors. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 63 15765187
2003 Expression and molecular pharmacology of the mouse CRTH2 receptor. The Journal of pharmacology and experimental therapeutics 63 12721327
2004 CRTH2 is a prominent effector in contact hypersensitivity-induced neutrophil inflammation. International immunology 60 15173122
2004 Ramatroban (BAY u 3405): a novel dual antagonist of TXA2 receptor and CRTh2, a newly identified prostaglandin D2 receptor. Cardiovascular drug reviews 58 15179446
2018 Inhibition of CRTH2-mediated Th2 activation attenuates pulmonary hypertension in mice. The Journal of experimental medicine 57 29970474
2003 15R-methyl-prostaglandin D2 is a potent and selective CRTH2/DP2 receptor agonist in human eosinophils. The Journal of pharmacology and experimental therapeutics 56 12490611
2016 Two Phase II randomized trials on the CRTh2 antagonist AZD1981 in adults with asthma. Drug design, development and therapy 55 27621597
2012 PGD2-CRTH2 pathway promotes tubulointerstitial fibrosis. Journal of the American Society of Nephrology : JASN 55 22997255
2008 CRTH2 antagonism significantly ameliorates airway hyperreactivity and downregulates inflammation-induced genes in a mouse model of airway inflammation. American journal of physiology. Lung cellular and molecular physiology 55 18757520
2005 Minor structural modifications convert the dual TP/CRTH2 antagonist ramatroban into a highly selective and potent CRTH2 antagonist. Journal of medicinal chemistry 55 15715457
2017 CRTH2 antagonists in asthma: current perspectives. Clinical pharmacology : advances and applications 52 29276415
2001 A novel surface molecule of Th2- and Tc2-type cells, CRTH2 expression on human peripheral and decidual CD4+ and CD8+ T cells during the early stage of pregnancy. Clinical and experimental immunology 51 11168006
2008 CRTH2 plays an essential role in the pathophysiology of Cry j 1-induced pollinosis in mice. Journal of immunology (Baltimore, Md. : 1950) 49 18390753
2021 PGD2 and CRTH2 counteract Type 2 cytokine-elicited intestinal epithelial responses during helminth infection. The Journal of experimental medicine 48 34283207
2016 Fevipiprant (QAW039), a Slowly Dissociating CRTh2 Antagonist with the Potential for Improved Clinical Efficacy. Molecular pharmacology 48 26916831
2008 A small molecule CRTH2 antagonist inhibits FITC-induced allergic cutaneous inflammation. International immunology 48 19066314
2020 Optimal identification of human conventional and nonconventional (CRTH2-IL7Rα-) ILC2s using additional surface markers. The Journal of allergy and clinical immunology 47 32032632
2006 A dominant role for chemoattractant receptor-homologous molecule expressed on T helper type 2 (Th2) cells (CRTH2) in mediating chemotaxis of CRTH2+ CD4+ Th2 lymphocytes in response to mast cell supernatants. Immunology 47 17067313
2014 Expression of DP2 (CRTh2), a prostaglandin D₂ receptor, in human mast cells. PloS one 46 25268140
2010 Pharmacological characterization of MK-7246, a potent and selective CRTH2 (chemoattractant receptor-homologous molecule expressed on T-helper type 2 cells) antagonist. Molecular pharmacology 45 20943773
2006 On the mechanism of interaction of potent surmountable and insurmountable antagonists with the prostaglandin D2 receptor CRTH2. Molecular pharmacology 45 16418339
2020 The Prostaglandin D2 Receptor CRTH2 Promotes IL-33-Induced ILC2 Accumulation in the Lung. Journal of immunology (Baltimore, Md. : 1950) 44 31900341
2007 A novel antagonist of CRTH2 blocks eosinophil release from bone marrow, chemotaxis and respiratory burst. Allergy 43 17714552
2005 9alpha,11beta-PGF2 and its stereoisomer PGF2alpha are novel agonists of the chemoattractant receptor, CRTH2. FEBS letters 41 16378605
2008 CRTH2-dependent, STAT6-independent induction of cedar pollen dermatitis. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 40 18477017
2010 The prostaglandin D₂ receptor CRTH2 is important for allergic skin inflammation after epicutaneous antigen challenge. The Journal of allergy and clinical immunology 39 20713302
2005 Delta12-prostaglandin D2 is a potent and selective CRTH2 receptor agonist and causes activation of human eosinophils and Th2 lymphocytes. Prostaglandins & other lipid mediators 39 15789622
2012 CRTH2 is a critical regulator of neutrophil migration and resistance to polymicrobial sepsis. Journal of immunology (Baltimore, Md. : 1950) 38 22544936
2010 Novel CRTH2 antagonists: a review of patents from 2006 to 2009. Expert opinion on therapeutic patents 38 20946089
2006 Targeting the prostaglandin D2 receptors DP and CRTH2 for treatment of inflammation. Current topics in medicinal chemistry 38 16918458
2017 The therapeutic potential of CRTH2/DP2 beyond allergy and asthma. Prostaglandins & other lipid mediators 37 28818625
2010 CRTH2 expression on T cells in asthma. Clinical and experimental immunology 37 20491797
2009 Genetic variability in CRTH2 polymorphism increases eotaxin-2 levels in patients with aspirin exacerbated respiratory disease. Allergy 36 19796209
2007 GATA3 up-regulation associated with surface expression of CD294/CRTH2: a unique feature of human Th cells. Blood 36 17234745
2016 Elevated levels of circulating CD4(+) CRTh2(+) T cells characterize severe asthma. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 35 27079298
2017 In Vivo Visualization of β-Cells by Targeting of GPR44. Diabetes 34 29208633
2006 Inhibition of PI3K and calcineurin suppresses chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2)-dependent responses of Th2 lymphocytes to prostaglandin D(2). Biochemical pharmacology 34 17196174
2019 Effects of an Oral CRTh2 Antagonist (AZD1981) on Eosinophil Activity and Symptoms in Chronic Spontaneous Urticaria. International archives of allergy and immunology 33 30879003
2010 3-Indolyl sultams as selective CRTh2 antagonists. Bioorganic & medicinal chemistry letters 33 20457519
2008 Antagonists of the prostaglandin D2 receptor CRTH2. Drug news & perspectives 33 18836589
2016 Eosinophils Contribute to Intestinal Inflammation via Chemoattractant Receptor-homologous Molecule Expressed on Th2 Cells, CRTH2, in Experimental Crohn's Disease. Journal of Crohn's & colitis 31 26928963
2021 ER-anchored CRTH2 antagonizes collagen biosynthesis and organ fibrosis via binding LARP6. The EMBO journal 30 34223653
2005 Identification of a potent and selective synthetic agonist at the CRTH2 receptor. Molecular pharmacology 30 15755909
2015 GPR44 is a pancreatic protein restricted to the human beta cell. Acta diabetologica 29 26467464
2009 Accumulation of CRTH2-positive leukocytes in human allergic nasal mucosa. Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology 29 19230460
2006 Differential regulation of the signaling and trafficking of the two prostaglandin D2 receptors, prostanoid DP receptor and CRTH2. European journal of pharmacology 29 17207480
2016 Depletion of major pathogenic cells in asthma by targeting CRTh2. JCI insight 28 27699264
2008 Expression and characterization of PGD2 receptors in chronic rhinosinusitis: modulation of DP and CRTH2 by PGD2. International archives of allergy and immunology 28 18802357
2018 Decreased CRTH2 Expression and Response to Allergen Re-stimulation on Innate Lymphoid Cells in Patients With Allergen-Specific Immunotherapy. Allergy, asthma & immunology research 27 30306748
2009 7-Azaindole-3-acetic acid derivatives: potent and selective CRTh2 receptor antagonists. Bioorganic & medicinal chemistry letters 27 19592244
2005 Identification of determinants of ligand binding affinity and selectivity in the prostaglandin D2 receptor CRTH2. The Journal of biological chemistry 27 16030019
2011 Dual functions of prostaglandin D2 in murine contact hypersensitivity via DP and CRTH2. The American journal of pathology 26 21703412
2019 Modulation of CRTh2 expression on allergen-specific T cells following peptide immunotherapy. Allergy 25 31077596
2015 CRTH2, a prostaglandin D2 receptor, mediates depression-related behavior in mice. Behavioural brain research 25 25698598
2013 Efficacy and safety of AZD1981, a CRTH2 receptor antagonist, in patients with moderate to severe COPD. Respiratory medicine 25 23827726
2011 Discovery of AMG 853, a CRTH2 and DP Dual Antagonist. ACS medicinal chemistry letters 25 24900313
2009 Tetrahydroquinoline derivatives as CRTH2 antagonists. Bioorganic & medicinal chemistry letters 25 19896843
2005 Small-molecule CRTH2 antagonists for the treatment of allergic inflammation: an overview. Expert opinion on investigational drugs 25 16022566
2007 A paracrine role for chemoattractant receptor-homologous molecule expressed on T helper type 2 cells (CRTH2) in mediating chemotactic activation of CRTH2+ CD4+ T helper type 2 lymphocytes. Immunology 24 17437532
2003 Gene structure and functional properties of mouse CRTH2, a prostaglandin D2 receptor. Biochemical and biophysical research communications 24 12878180
2008 Prostaglandin D2 receptors DP and CRTH2 in the pathogenesis of asthma. Current molecular medicine 23 18691063
2008 Antagonism of CRTH2 ameliorates chronic epicutaneous sensitization-induced inflammation by multiple mechanisms. International immunology 23 19066315
2003 Differential expression of CCR5 and CRTH2 on infiltrated cells in colonic mucosa of patients with ulcerative colitis. Journal of gastroenterology and hepatology 23 12911667
2005 CRTH2-specific binding characteristics of [3H]ramatroban and its effects on PGD2-, 15-deoxy-Delta12, 14-PGJ2- and indomethacin-induced agonist responses. European journal of pharmacology 22 16256979
2004 The Th2 response as monitored by CRTH2 or CCR3 expression is severely decreased during septic shock. Clinical immunology (Orlando, Fla.) 22 15507393

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