C-type lectin SIGN-R1 has a role in experimental colitis and responsiveness to lipopolysaccharide.
نویسندگان
چکیده
Pathogen recognition receptors (PRRs) function to maintain the balance between controlled responses to pathogens and uncontrolled innate immune activation leading to inflammation. In the context of commensal bacteria and the etiology of inflammatory bowel disease, although a role for the TLRs is known, there is a less defined function for C-type lectin receptors (CLRs). We demonstrate that mice deficient ((-/-)) in the CLR specific intracellular adhesion molecule-3 grabbing nonintegrin homolog-related 1 (SIGN-R1) (CD209b) have reduced susceptibility to experimental colitis, with a reduction in the disease severity, colon damage, and levels of the proinflammatory cytokines IL-1beta, TNF-alpha, and IL-6. To determine whether SIGN-R1(-/-) mice had a systemic defect in innate activation, we examined the responsiveness of macrophages from SIGN-R1(-/-) mice to TLR ligands. SIGN-R1(-/-) peritoneal macrophages, but not bone marrow-derived macrophages, have a specific defect in IL-1beta and IL-18 production, but not other cytokines, in response to the TLR4 ligand LPS. In vivo SIGN-R1(-/-) mice had significantly reduced susceptibility to LPS-induced shock. To address the synergistic relationship between SIGN-R1 and TLR4 in the context of experimental colitis, SIGN-R1/TLR4(-/-) mice were generated. SIGN-R1/TLR4(-/-) mice displayed reduced susceptibility to experimental colitis relative to severity of disease observed in wild-type or TLR4(-/-) mice. The in vivo use of a blocking mAb confirmed a functional role for SIGN-R1 in LPS-induced shock and experimental colitis. These data indicate a role for SIGN-R1 in the regulation of inflammation in a model of experimental colitis and illustrate that SIGN-R1 is a critical innate factor in response to LPS.
منابع مشابه
Lipopolysaccharide Experimental Colitis and Responsiveness to C-Type Lectin SIGN-R1 Has a Role in
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عنوان ژورنال:
- Journal of immunology
دوره 184 5 شماره
صفحات -
تاریخ انتشار 2010