Increasing dietary nutrient levels modulates colon immune adaptation and alleviates inflammation in the epithelial heterogeneous nuclear ribonucleoprotein I (Hnrnp I ) knockout mice

Heterogeneous nuclear ribonucleoprotein I (HNRNP I) is an RNA-binding protein essential for neonatal immune adaptation by downregulating interleukin-1 receptor-associated kinase (IRAK1) in toll-like receptor (TLR)-mediated NF-KB signaling pathways. TLR-mediated NF-KB is associated with chronic inflammation, including the development of inflammatory bowel diseases. Meanwhile, dietary protein intake is one of the major concerns for in-dividuals with inflammatory bowel diseases. The present study aims to investigate the effects of a protein-enriched diet on intestinal inflammation and immune responses in a mouse model with aberrant NF-KB signaling in the colon. A transgenic mouse model with intestinal-epithelial-cell (IEC) specific Hnrnp I knocked out was used to investigate the effects of protein intake on the immune system in the colon. A control diet (CON) and a nutrient-dense modified diet (MOD) were fed to both the wild-type (WT) and the knockout (KO) male mice for 14 weeks. Inflammatory markers and colonic immune responses were examined, with gene expression and protein expression levels analyzed. IEC-specific Hnrnp I knocked out mice had significantly increased expression of the active NF-KB subunit, P65, in their colons. There was a concomitant induction of mRNA expression of Il1 & beta;, Il6, Cxcl1, and Ccl2. The number of CD4+ T cells in the distal colon was also increased in the KO mice. The results confirmed that KO mice had proinflammatory responses with aberrant NF-KB signaling in the colon. Importantly, increased nutrient density in their diets attenuated colon inflammation by decreasing the expression of proinflammatory cytokines, reducing P65 translocation, downregulating IRAK1, and limiting the number of CD4+ T cells recruited in Hnrnp I KO mice colon. In summary, this study found that a diet with increased nutrient density relieved the inflammation induced by knockout of Hnrnp I , attributable partially to the reduced expression of inflammatory and immune-modulating cytokines in the mouse distal colon. & COPY; 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )

Automated summary

This study found that a diet with increased nutrient density relieved the inflammation induced by knockout of Hnrnp I, partially due to the reduced expression of inflammatory and immune-modulating cytokines in the mouse distal colon.