CDB25:0004501 WNT5A — TLR2

Experimentally validated in Human; Orthology-inferred in Mouse, Rat, Frog, Zebrafish, Chicken, Macaque, Pig, Dog, Cow, Chimp, Horse, Marmoset, Sheep

Title

Journal:; Year Published:

Abstract

Wnt5a is a TLR2/4-ligand that induces tolerance in human myeloid cells.

Communications biology, 2019; PubMed, Homo sapiens WNT5A — Homo sapiens TLR2

ABSTRACT: Innate immune responses are rapid, dynamic and highly regulated to avoid overt reactions. This regulation is executed by innate immune tolerance mechanisms that remain obscure. Wnt5a is a signalling protein mainly involved in developmental processes and cancer. The effect of Wnt5a on inflammatory myeloid cells is controversial. Here, we combine primary cell cultures, in vitro binding studies, mass spectrometry and Drosophila protein modelling to show that Wnt5a is a direct ligand of toll-like receptor (TLR) 2 and 4. The binding promotes a MyD88-non-canonical nuclear factor of kappa B (NFκB) and AP-1 signalling cascade, with contradictory profiles in mouse (pro-inflammatory) and human (anti-inflammatory) myeloid immune cells. These data reveal that the true nature of Wnt5a in inflammatory cells, is to regulate TLR signals, and in human myeloid cells it acts as an endogenous, tolerance-associated molecular pattern (TAMP), inducing IL-10 and innate immune tolerance.

Basic Information on WNT5A

Ligand Name: Wnt family member 5A

Other Symbols: hWNT5A

Ligand Location: secreted based on hpa, perplexity, uniprot

HGNC Gene Symbol Report: WNT5A

GeneCards: WNT5A

HGNC Gene Group: Receptor ligands: Wnt family

Functional Annotations for WNT5A

Gene Ontologies: PAN-GO, AmiGO 2

Expression Profile: Human Protein Atlas (RNA and protein), Human Cell Atlas (RNA), GEPIA cancer vs normal (RNA), GeneCards (RNA and protein)

Disease Annotations: MalaCards, OMIM, Open Targets Platform, DISEASES (text mining), AI summary (LLM)

Interactions with other Receptors for WNT5A

WNT5A — FZD1 ・ WNT5A — FZD2 ・ WNT5A — FZD4 ・ WNT5A — FZD5 ・ WNT5A — FZD6 ・ WNT5A — FZD7 ・ WNT5A — FZD8 ・ WNT5A — LRP5 ・ WNT5A — MCAM ・ WNT5A — ROR1 ・ WNT5A — ROR2 ・ WNT5A — RYK ・ WNT5A — FZD3 ・ WNT5A — APP ・ WNT5A — FZD9 ・ WNT5A — LRP6 ・ WNT5A — PTK7 ・ WNT5A — TLR4 ・ WNT5A — TMEM67 ・ WNT5A — VANGL2

Basic Information on TLR2

Receptor Name: toll like receptor 2

Other Symbols: TIL4, CD282

Receptor Location: cell membrane based on hpa, perplexity

HGNC Gene Symbol Report: TLR2

GeneCards: TLR2

HGNC Gene Group: TIR domain containing, CD molecules

Functional Annotations for TLR2

Gene Ontologies: PAN-GO, AmiGO 2

Expression Profile: Human Protein Atlas (RNA and protein), Human Cell Atlas (RNA), GEPIA cancer vs normal (RNA), GeneCards (RNA and protein)

Disease Annotations: MalaCards, OMIM, Open Targets Platform, DISEASES (text mining), AI summary (LLM)

Interactions with other Ligands for TLR2

BGN — TLR2 ・ HSP90B1 — TLR2 ・ RNASE2 — TLR2 ・ SFTPA1 — TLR2 ・ VCAN — TLR2 ・ ZG16B — TLR2 ・ ANXA2 — TLR2 ・ DCN — TLR2 ・ PRG4 — TLR2 ・ CCN1 — TLR2 ・ HMGB1 — TLR2 ・ HSPA1A — TLR2 ・ S100A8 — TLR2 ・ SAA1 — TLR2 ・ SFTPA2 — TLR2 ・ SFTPD — TLR2