CDB25:0003902 LGALS9 — TLR4

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

Title

Journal:; Year Published:

Abstract

Galectin-9 regulates the threshold of B cell activation and autoimmunity.

eLife, 2021; PubMed, Mus Musculus Lgals9 — Mus Musculus Tlr4

ABSTRACT: Despite the mechanisms of central and peripheral tolerance, the mature B cell compartment contains cells reactive for self-antigen. How these cells are poised not to respond and the mechanisms that restrain B cell responses to low-affinity endogenous antigens are not fully understood. Here, we demonstrate a critical role for the glycan-binding protein galectin-9 in setting the threshold of B cell activation and that loss of this regulatory network is sufficient to drive spontaneous autoimmunity. We further demonstrate a critical role for galectin-9 in restraining not only conventional B-2 B cells, but also innate-like B-1a cells. We show that galectin-9-deficient mice have an expanded population of B-1a cells and increased titers of B-1a-derived autoantibodies. Mechanistically, we demonstrate that galectin-9 regulates BCR and distinct TLR responses in B-1a cells, but not B-1b cells, by regulating the interaction between BCR and TLRs with the regulatory molecules CD5 and CD180, respectively. In the absence of galectin-9, B-1a cells are more readily activated and secrete increased titers of autoantibodies that facilitate autoantigen delivery to the spleen, driving autoimmune responses.

Basic Information on LGALS9

Ligand Name: galectin 9

Other Symbols: LGALS9A

Ligand Location: secreted based on hpa, perplexity, uniprot

HGNC Gene Symbol Report: LGALS9

GeneCards: LGALS9

HGNC Gene Group: Receptor ligands, Galectins

Functional Annotations for LGALS9

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 LGALS9

LGALS9 — CD44 ・ LGALS9 — HAVCR2 ・ LGALS9 — BCR ・ LGALS9 — CD180 ・ LGALS9 — CD40 ・ LGALS9 — CLEC7A ・ LGALS9 — IGHM ・ LGALS9 — PTPRC ・ LGALS9 — VSIR

Basic Information on TLR4

Receptor Name: toll like receptor 4

Other Symbols: hToll, CD284, TLR-4, ARMD10

Receptor Location: cell membrane based on hpa, perplexity, uniprot

HGNC Gene Symbol Report: TLR4

GeneCards: TLR4

HGNC Gene Group: TIR domain containing, CD molecules

Functional Annotations for TLR4

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 TLR4

BGN — TLR4 ・ DEFB4A — TLR4 ・ HSP90B1 — TLR4 ・ HSPA1A — TLR4 ・ S100A8 — TLR4 ・ S100A9 — TLR4 ・ SFTPD — TLR4 ・ ZG16B — TLR4 ・ DCN — TLR4 ・ FGA — TLR4 ・ FGB — TLR4 ・ FGG — TLR4 ・ PRG4 — TLR4 ・ AHSG — TLR4 ・ ANXA2 — TLR4 ・ CCN1 — TLR4 ・ CIRBP — TLR4 ・ CXCL10 — TLR4 ・ FCN2 — TLR4 ・ HMGB1 — TLR4 ・ HP — TLR4 ・ HSPA4 — TLR4 ・ MMP9 — TLR4 ・ NAMPT — TLR4 ・ RBP4 — TLR4 ・ RETN — TLR4 ・ S100A1 — TLR4 ・ S100A12 — TLR4 ・ S100A4 — TLR4 ・ SAA1 — TLR4 ・ SFTPA1 — TLR4 ・ TNC — TLR4 ・ WNT5A — TLR4