MD-1 deficiency attenuates dextran sodium sulfate (DSS)-induced colitis through modulating the function of colonic lamina propria dendritic cells

Mol Immunol. 2016 Jul:75:1-10. doi: 10.1016/j.molimm.2016.05.008. Epub 2016 May 19.

Abstract

Available evidence suggests that both dysregulated innate and adaptive immune pathways contribute to the aberrant intestinal inflammatory response in patients with inflammatory bowel disease (IBD). Myeloid Differentiation 1 (MD-1), also known as Lymphocyte Antigen 86 (Ly86), a secreted protein interacting with radioprotective 105 (RP105), plays an important role in Toll-like receptor 4 (TLR4) signaling pathway. Previous studies showed that MD-1 may be involved in the (patho) physiological regulation of the innate immune system and inflammation. In this study, we reported for the first time that MD-1 mRNA expression was up-regulated in both human IBD patients and DSS-treated WT mice. We showed that MD-1(-/-) mice were less susceptible to the development of colitis than WT controls as demonstrated by significantly reduced weight loss, disease activity index, colon histological scores, cellular infiltration and expression of inflammatory mediators. In addition, mucosal barrier function seemed to be intact in response to the loss of MD-1. Finally, lamina propria dendritic cells (LPDCs) from the colon of MD-1(-/-) mice after DSS exposure not only decreased in number but also significantly down-regulated the expression of surface maturation co-stimulatory molecules MHC-II, CD40 and CD86 compared with those from WT mice. Taken together, our results reveal that MD-1 deficiency is of critical importance in down-regulating induction and progression of DSS colitis, thereby suggesting that MD-1 might be a target for future interventional therapies of IBD.

Keywords: Colitis; Dendritic cells; Dextran sodium sulfate; MD-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Surface / immunology*
  • Antigens, Surface / metabolism
  • Colitis / immunology*
  • Colitis / metabolism
  • Colitis / pathology
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Dextran Sulfate / toxicity
  • Disease Models, Animal
  • Flow Cytometry
  • Humans
  • Immunohistochemistry
  • Inflammatory Bowel Diseases / immunology
  • Inflammatory Bowel Diseases / metabolism
  • Inflammatory Bowel Diseases / pathology
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / pathology
  • Membrane Glycoproteins / immunology*
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Knockout
  • Real-Time Polymerase Chain Reaction

Substances

  • Antigens, Surface
  • LY86 protein, human
  • Ly86 protein, mouse
  • Membrane Glycoproteins
  • Dextran Sulfate