Role of the C-Type Lectin Receptors MCL and DCIR in Experimental Colitis

Abstract

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract. Though its exact etiology is still unclear, it is proposed that an imbalance in the intestinal homeostasis leads to a disturbed interaction between commensal microbiota and the mucosal immune system. Previous studies have shown that both innate and adaptive immunity are involved in an overwhelming colon inflammation, and thus contribute to the pathogenesis of IBD. In innate immunity, several pattern recognition receptors such as Toll-like receptors, NOD-like receptors or C-type lectin receptors (CLRs) are involved in IBD pathogenesis. Myeloid CLRs are mainly expressed by antigen-presenting cells and bind to glycan structures present on self or foreign antigens. The Macrophage-restricted C-type lectin (MCL) and the Dendritic cell immunoreceptor (DCIR) are two poorly characterized members of the CLR family. In this study, we investigated the role of MCL and DCIR in the pathogenesis of murine colitis. Both CLRs bound to intestinal microbiota to a different extent. They modulated the production of pro-inflammatory cytokines by antigen-presenting cells upon stimulation with heat-killed microbiota and impacted subsequent T cell responses. To analyze whether MCL and DCIR contribute to the pathogenesis of IBD, the dextran sulfate sodium (DSS) murine colitis model was employed. MCL−/− as well as DCIR−/− mice exhibited only a slightly increased severity of disease compared to wild-type mice indicating a limited role for MCL and DCIR in the regulation of intestinal immunity.

Intestinal epithelial cells and T cells differentially recognize and respond to Candida albicans yeast and hypha

“…It is well established that switching of C. albicans from yeast to hypha is crucial for tissue invasion, and that glycans expressed on the surface of C. albicans are crucial for proper recognition and response by epithelial cells mostly via recognition by TLRs and C‐type lectin receptors . Here we demonstrate a clear upregulation of TLR2 and TLR4 in epithelial cells and T cells, upon stimulation with yeast and hypha, suggesting a possible mode of action for fungal recognition.…”

“…Possible candidates for fungal recognition by adaptive cells could be C‐type lectin receptors , DC‐SIGN , mannose receptor , or galectins . Recently, C‐type lectin receptors have been suggested to initiate intestinal inflammation in both humans and mice , via fungal recognition and act as adjuvants to stimulate both the innate and adaptive immune reaction. Noteworthy, we used soluble laminarin.…”

Rheumatoid arthritis: identifying and characterising polymorphisms using rat models

“…The APLEC gene cluster is also associated with motor neuron survival after traumatic nerve root injury (Lindblom et al, 2013). In knockout mice, these different receptor genes have been linked to the development of arthritis (Fujikado et al, 2008), to experimental colitis (Hütter et al, 2014; Tokieda et al, 2015) and to EAE, as well as being involved in the response to infection (Uto et al, 2016). Further studies are needed to better understand how the APLEC region is involved in immune regulation and in inflammation in humans.…”

Myeloid C-type lectin receptors in skin/mucoepithelial diseases and tumors

“…Mice lacking this molecule develop more severe inflammation after DSS‐treatment, accompanied with impaired IL‐10 secretion . Although MCL and DCIR also bind some intestinal commensal microbiota, mice deficient in these molecules develop slightly more severe DSS–induced colitis . Another report showed that DCIR‐deficient mice develop even milder colitis, with reduced neutrophil‐attracting chemokine MIP‐2 and decreased accumulation of neutrophils .…”