A novel anti-inflammatory function of Thy1 stromal cells in colitis 

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B580
Abstract ID: 5032

Presenting Author:
Alvaro Torres-Huerta , Postdoc at Indiana Univ. Sch. of Med.

Abstract:

Background: Inflammatory Bowel Disease (IBD) is a complex immune disorder affecting the gastrointestinal tract. Stromal cells play a crucial role modulating the immune response. We evaluated the function of the Thy1 positive stromal population, specifically elucidating its role in the context of the innate immune system within the framework of IBD.

Methods: We created a mouse model that develops 100% penetrant, early-onset colitis in the absence of adaptive immunity. Transgenic mice expressing the TNFAIP3 (A20) gene under the villin promoter, (Villin-tgA20), crossed with RAG1-/- mice (villin-tgA20 x RAG1-/-; aka TRAG) develop innate colitis. To study ILCs and Thy1 functions in colitis we used IL2Rg-/- and Thy1-/- mice, crossed with TRAG (IL2Rg-/- x TRAG, and Thy1-/- x TRAG). IL2Rg-/- x TRAG, and Thy1-/- x TRAG were injected with anti-Thy1 antibody and assessed for prevention of colitis.

Results: In absents of ILCs (IL2Rg-/- x TRAG) and Thy1 (Thy1-/- x TRAG) colitis persists. Treatment with anti-Thy1 antibody prevents colitis in TRAG and IL2Rg-/- x TRAG, but not in Thy1-/- x TRAG, mice.  Colitis in TRAG, IL2Rg-/- x TRAG, and Thy1-/- x TRAG, is characterized by an abundance of neutrophils and inflammatory monocytes. In the colon of IL2Rg-/- x TRAG mice we observed a Thy1 positive population that expressed podoplanin but not CD31. Thus, Thy1 is a functional molecule and stimulation of stromal cell Thy1 induces an anti-inflammatory response that prevents IBD.