Retinoid Orphan Receptor Gamma T (RORgT) Promotes Inflammatory Eosinophilia but is Dispensable for Innate Immune-Mediated Colitis

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B203
Abstract ID: 4414

Presenting Author:
Katelyn Ruley Haase , PhD Student at Univ. of Notre Dame, Indiana Univ. Sch. of Med.

Abstract:

Inflammatory bowel diseases (IBD) result from uncontrolled intestinal inflammation leading to loss of function. Innate and adaptive immunity contribute to IBD inflammation as both reciprocally activate each other in a forward feedback loop. To better understand innate immune contributions to IBD we developed a model of spontaneous, early-onset colitis that occurs in the absence of adaptive immunity by crossing villin-TNFAIP3 mice to RAG1-/- mice (TRAGs). This model is driven by microbes and features increased leukocyte and innate lymphoid cells (ILC) numbers in the colonic mucosa.

To investigate roles of type 3 ILC (ILC3) in innate immune colitis, we crossed TRAG mice to retinoid orphan receptor gamma t deficient (Rorgt-/-) mice. Rorgt-/- x TRAGs exhibited markedly reduced eosinophilia in the colonic mucosa but colitis persisted. Rorgt-/- x TRAG colitis was characterized by increased intestinal mucosal infiltration by neutrophils, inflammatory monocytes, macrophages and other innate cells. RNA sequence profiles of Rorgt-/- x TRAGs were consistent with a lack of ILC3 and ILC3-derived cytokines, reduced antimicrobial factors, increased activation of epithelial repair processes and reduced activation of epithelial cell STAT3. Rorgt-/- x TRAG colitis was ameliorated by antibiotic treatment, indicating microbial contributions to ILC3-independent colitis. Thus, Rorgt promotes eosinophilia, but Rorgt and Rorgt-dependent ILC3 are dispensable for TRAG mouse innate colitis.