"Esophageal epithelial cells present antigen on MHCII in an IFNy and Promoter IV-dependent manner"

Eric M. Rodriguez-Lopez, Julianna Dilollo, Laurence C. Eisenlohr and David A. Hill

Presentation of antigen on MHCII by epithelial cells may contribute to inflammatory gastrointestinal diseases such as Eosinophilic Esophagitis (EoE). However, the regulation and function of MHCII in esophageal epithelial cells (EECs), and the contribution of EEC-intrinsic MHCII expression to in vivo models of esophageal disease, have not been evaluated. To do so, we investigated the contribution of IFNy to EEC MHCII expression by treating C57BL/6J, F1 hybrid, and promoter IV-deficient (pIV-/-) mice (lack non-hematopoietic MHCII) with PBS or 1x105 U of IFNy intravenously. We also evaluated EEC MHCII expression during an established EoE mouse model (MC903/OVA). Esophagi were processed into single cell suspensions for flow cytometric analysis of MHCII expression on EECs. For F1 mice, we used the Y-Ae monoclonal antibody system to detect the E alpha 52-68 I-Ab peptide-MHC complex. We observed statistically significant 2-fold increases in MHCII expression by EECs after treatment of C57BL/6J mice with IFNy as compared with PBS (20.94%±3.58 vs 9.16%±0.88, p=0.0127 by unpaired t-test). IFNy-treated F1 mice also had 2-fold significantly increased expression of Y-Ae. The IFNy-induced effect was ablated in pIV-/- mice. Finally, we observed increased MHCII expression in mice with EoE-like inflammation, compared to non-sensitized controls (55.63±6.69 vs 23.67±3.82, p=0.0410 by ordinary one-way ANOVA). In conclusion, antigen presentation on MHCII by EECs is tightly regulated by IFNy at the epigenetic level. Increased MHCII by EECs in mice with EoE suggests a possible role in this disease. Future studies will dissect the specific contributions of MHCII on EECs to EoE immunopathology.