P031 - ENTERIC GLIA SHARE CHARACTERISTICS WITH ANTIGEN PRESENTING CELLS AND MAY ALTER SERUM CHEMOKINE LEVELS DURING NEUROINFLAMMATION
(Room Poster Hall)
19 Jan 18
5:30 PM
-
7:00 PM
Tracks:
Clinical and Research Challenges
The enteric nervous system (ENS) is intrinsic to the gastrointestinal (GI) tract and controls essential gut functions such as motility, blood flow and secretions. Injury to the ENS contributes to the pathophysiology of common GI disorders including irritable bowel syndrome and the inflammatory bowel diseases. Recent data show that enteric glia, a type of peripheral glia that surround enteric neurons, contribute to neuroinflammation and express major histocompatibility complex class II (MHC II) during disease. The significance of enteric glial MHC II expression in the pathophysiology of gut inflammation is unknown. Here, we tested the hypothesis that antigen presentation by enteric glia contributes to a pro-inflammatory environment during ENS injury. We tested our hypothesis by generating mice with a targeted ablation of MHC II in glia (Sox10CreERT2::IABfl/fl). Tissue cultures of wild-type glia in the colonic myenteric plexus upregulate MHC II expression 1.85 fold by immunofluorescence after 18 hour incubation with 10ng/mL interferon-gamma. Similarly, myenteric glia increase MHC II expression 2.14 fold in vivo following 6 hour exposure to interferon-gamma and lipopolysaccharide. In vivo exposure to interferon-gamma and lipopolysaccharide shifts the serum cytokine profile to a more pro-inflammatory state, with significant increases in serum levels of G-CSF, IL-6, CXCL1 (p<0.0001), and M-CSF (p<0.0005). In addition, animals with ablated glial MHC II demonstrate a diminished cytokine response to interferon-gamma and lipopolysaccharide, as there are significantly lower levels of serum CXCL2 (p<0.001) and IP-10 (p<0.05) compared to wildtype counterparts. Serum levels of CCL4 and CCL5 are also decreased, but do not reach statistical significance. Our results suggest that enteric glial cells share characteristics with antigen presenting cells, and may influence serum chemokine levels based on their MHC II expression status.