| 2013 |
TAFA4 is a specific marker of C-low-threshold mechanoreceptors (C-LTMRs). TAFA4-null mice exhibit enhanced mechanical and chemical hypersensitivity following inflammation and nerve injury, with increased excitability of spinal cord lamina IIi neurons. Intrathecal or bath application of recombinant TAFA4 protein reversed this increased excitability, and intrathecal administration strongly reversed carrageenan-induced mechanical hypersensitivity in wild-type mice, establishing an analgesic role for C-LTMR-derived TAFA4 in modulating neuronal excitability and somatic sensation thresholds. |
Genetic labeling, electrophysiological recordings, TAFA4-null mouse model (loss-of-function), intrathecal and bath application of recombinant TAFA4 protein |
Cell reports |
High |
24139797
|
| 2014 |
FAM19A4 (TAFA4) is a ligand of formyl peptide receptor 1 (FPR1). The mature protein is composed of 95 amino acids. FAM19A4 shows chemotactic activity on macrophages, enhances macrophage phagocytosis of zymosan (with increased Akt phosphorylation), and increases reactive oxygen species (ROS) release. These activities were demonstrated by receptor internalization assays, radioligand binding assays, and receptor blockage experiments. |
Receptor internalization assay, radioligand binding assay, receptor blockage, in vitro chemotaxis assay, in vivo phagocytosis assay, western blot for Akt phosphorylation |
Cellular & molecular immunology |
High |
25109685
|
| 2021 |
Sensory neuron-derived TAFA4, produced specifically by C-low threshold mechanoreceptors (a subset of GINIP+ neurons), promotes the tissue-repair function of dermal macrophages. In vivo, TAFA4-deficient mice showed defective tissue regeneration and dermal fibrosis after UV-induced skin damage. TAFA4 modulates the inflammatory profile of macrophages directly in vitro. A TAFA4-IL-10 axis was identified whereby TAFA4 promotes IL-10 production by dermal macrophages and ensures survival and maintenance of IL-10+TIM4+ dermal macrophages, reducing inflammation and promoting tissue regeneration. |
Conditional sensory neuron ablation, Tafa4-deficient mouse model, in vitro macrophage stimulation, in vivo UV-skin damage model, flow cytometry, histology |
Nature |
High |
34012116
|
| 2021 |
TAFA4 reverses inflammatory, postoperative, and spared nerve injury (SNI)-induced mechanical hypersensitivity through functional low-density lipoprotein receptor-related proteins (LRPs), as their inhibition by RAP (receptor-associated protein) dose-dependently abolished TAFA4's antihypersensitive actions. SNI selectively decreases A-type K+ current (IA) in spinal lamina II outer excitatory interneurons and alters Ih in lamina II inner inhibitory interneurons; these ion current alterations were rescued by TAFA4 in an LRP-dependent manner. |
In vivo mechanical hypersensitivity assays, pharmacological inhibition (RAP), electrophysiological recordings of spinal interneuron ion currents, multiple pain models (inflammatory, postoperative, SNI) |
Cell reports |
High |
34706225
|
| 2022 |
TAFA4 activates dendritic cells (DCs) in airway tissues, inducing IL-10 expression via the FPR1-MyD88-AKT signaling pathway. TAFA4 also promotes activities of c-Maf inducing protein in DCs. Co-administration of TAFA4 with allergen immunotherapy induced antigen-specific Tr1 regulatory T cells and attenuated allergic rhinitis response in mice. |
Mouse allergic rhinitis model, DC stimulation in vitro, signaling pathway inhibitor assays (FPR1-MyD88-AKT), flow cytometry for Tr1 cells |
NPJ vaccines |
Medium |
36316414
|
| 2023 |
TAFA4 modulates FcεRI expression in mast cells through the TAFA4-PTEN-PU.1 signaling axis, which restricts transcription of Fcer1g (FcεRI γ gene). TAFA4 suppressed antigen-related mast cell activation and attenuated experimental allergic rhinitis. Negative correlation between TAFA4 and tryptase levels in nasal secretions from allergic rhinitis patients was observed. |
ELISA (nasal secretions from patients), mouse allergic rhinitis model, in vitro mast cell stimulation, transcriptional analysis of Fcer1g, PTEN-PU.1 pathway interrogation |
Clinical and experimental immunology |
Medium |
36368013
|
| 2025 |
TAFA4 overexpression in dorsal root ganglia (DRG) ameliorates neuropathic pain by promoting macrophage M2 polarization in the DRGs. Mechanistically, TAFA4 modulates macrophage function in a lipoprotein receptor-related protein 1 (LRP1)-dependent manner. TAFA4 overexpression (via scAAV) increased IL-10 concentrations in DRG and inhibited pro-inflammatory mediators after chronic constriction injury. |
Chronic constriction injury (CCI) rat model, scAAV-mediated TAFA4 overexpression, flow cytometry, western blot, immunofluorescence, ELISA |
Neurochemistry international |
Medium |
40381955
|
| 2026 |
FAM19A4 enhances neutrophil reactive oxygen species (ROS) production specifically through p38 MAPK signaling activation. FAM19A4 deficiency (Fam19a4 knockout mice) in a cecal ligation and puncture (CLP) sepsis model improved survival and reduced multiorgan injury, reduced neutrophil and macrophage counts in lungs and liver, and decreased neutrophil extracellular trap (NET) formation. In vitro, FAM19A4 enhanced neutrophil phagocytosis and ROS generation but did not affect LPS-induced chemotaxis. |
Fam19a4 knockout mouse CLP sepsis model, bulk RNA sequencing, western blot, p38 MAPK inhibitor (SB203580) treatment, bioluminescence ROS tracking, flow cytometry, in vitro neutrophil assays |
Acta biochimica et biophysica Sinica |
Medium |
41517951
|
| 2026 |
TAFA4 acts as a neuron-derived mediator in intervertebral disc degeneration (IVDD). GINIP+ sensory neurons secrete TAFA4 in degenerative discs. In vitro, GINIP+ neurons promoted macrophage M2 polarization and IL-10 production while suppressing TNF-α and IL-1β; these effects were reversed by TAFA4 knockdown. TAFA4 attenuated ROS-dependent NLRP3 inflammasome activation in macrophages. |
In vivo IVDD model with lentiviral TAFA4 knockdown, in vitro neuron-macrophage co-culture, flow cytometry, immunofluorescence, ELISA, western blot |
Neurospine |
Medium |
41666872
|
| 2026 |
During herpes simplex virus type 1 infection, sensory neurons produce TAFA4. In infected dorsal root ganglia (DRGs), a TAFA4-IL-10 pathway promotes the resolution of inflammation after viral clearance, functioning independently from substance P actions in skin. This neuroimmune regulatory pathway reduces detrimental impact of infection on host fitness without directly altering pathogen elimination. |
HSV-1 mouse infection model, tissue-specific analysis of DRG vs. skin, genetic and pharmacological dissection of SP and TAFA4 pathways |
Immunity |
Medium |
41747735
|
| 2024 |
In a Shank3 mouse model of autism, C-fiber low-threshold mechanoreceptors (C-LTMRs) are hyporesponsive and TAFA4 is transcriptomically downregulated. TAFA4 injection reduced spontaneous scratching response to skin deformation but failed to restore itch sensitivity, suggesting TAFA4 modulates one component of mechanical itch but not the full alloknesis pathway. |
Ex vivo electrophysiology of C-LTMRs, transcriptomic analysis, TAFA4 pharmacological injection, Shank3 ΔC/ΔC mouse model |
bioRxivpreprint |
Low |
bio_10.1101_2024.12.29.630575
|