Inflammatory bowel disease is a condition of acute and chronic inflammation of
the gut. An important factor contributing to pathogenesis is a dysregulated
mucosal immunity against commensal bacteria and fungi. Host pattern-
recognition receptors (PRRs) sense commensals in the gut and are involved in
maintaining the balance between controlled responses to pathogens and
overwhelming innate immune activation. C-type lectin receptors (CLRs) are PRRs
recognizing glycan structures on pathogens and self-antigens. Here we examined
the role of the murine CLR specific intracellular adhesion molecule-3 grabbing
non-integrin homolog-related 3 (SIGNR3) in the recognition of commensals and
its involvement in intestinal immunity. SIGNR3 is the closest murine homolog
of the human dendritic cell-specific intercellular adhesion
molecule-3-grabbing non-integrin (DC-SIGN) receptor recognizing similar
carbohydrate ligands such as terminal fucose or high-mannose glycans. We
discovered that SIGNR3 recognizes fungi present in the commensal microbiota.
To analyze whether this interaction impacts the intestinal immunity against
microbiota, the dextran sulfate sodium-induced colitis model was employed.
SIGNR3(-/-) mice exhibited an increased weight loss associated with more
severe colitis symptoms compared to wild-type control mice. The increased
inflammation in SIGNR3(-/-) mice was accompanied by a higher level of TNF-α in
colon. Our findings demonstrate for the first time that SIGNR3 recognizes
intestinal fungi and has an immune regulatory role in colitis