Dietary protein ameliorates goblet cell loss and modifies inflammatory responses in the colon of hnRNPI knockout mouse

Abstract

Heterogeneous nuclear ribonucleoprotein I (hnRNPI) is an essential RNA binding protein that plays a critical role in regulating neonatal immune adaptation through downregulation of interleukin-1 receptor-associated kinase (IRAK1) in toll-like receptor (TLR)-mediated NF-κB signaling. Transgenic mice with hnRNPI specifically knockout in intestinal epithelial cells (IECs) develop spontaneous colitis at an early age. Moderate dietary protein has been demonstrated to exert beneficial effects for individuals with colitis, however, mechanisms of how dietary protein impacts inflammation development and immune responses are still unclear. This study aims to examine the potential roles of dietary protein in regulating goblet cells and inflammatory responses in a mouse model with IECs-specific hnRNPI knockout‐induced colitis. Physiological outcomes were assessed by body weight, growth rate, colon parameters and histology analysis. Goblet cells were quantified by staining. Relative mRNA levels of inflammation- and goblet cell-associated genes were examined using quantitative real-time PCR. CD4+ T cell subpopulations in the distal colon were measured by flow cytometry analysis. The results demonstrated that medium dietary protein prevents goblet cell loss and alters inflammatory responses with an increase in IL17- IFNγ- CD4+ T cells. Notably, we found that primary and dominant immune responses in hnRNPI knockout mice were significant increases in regulatory T cells and IL17- IFNγ- CD4+ T cells in the colon. Collectively, these results demonstrated that medium dietary protein ameliorates goblet cell loss and modifies inflammatory responses with an increase in IL17- IFNγ- CD4+ T cells in the colon of IECs- specific hnRNPI knockout mouse.