title: hnRNP I regulates neonatal immune adaptation and prevents colitis and colorectal cancer.
abstract: The intestinal epithelium plays a critical role in host-microbe homeostasis by sensing gut microbes and subsequently initiating proper immune responses. During the neonatal stage, the intestinal epithelium is under immune repression, allowing the transition for newborns from a relatively sterile intra-uterine environment to one that is rich in foreign antigens. The mechanism underlying such immune repression remains largely unclear, but involves downregulation of IRAK1 (interleukin-1 receptor-associated kinase), an essential component of toll-like receptor-mediated NF-κB signaling. We report here that heterogeneous nuclear ribonucleoprotein I (hnRNPI), an RNA binding protein, is essential for regulating neonatal immune adaptation. We generated a mouse model in which hnRNPI is ablated specifically in the intestinal epithelial cells, and characterized intestinal defects in the knockout mice. We found that loss of hnRNPI function in mouse intestinal epithelial cells results in early onset of spontaneous colitis followed by development of invasive colorectal cancer. Strikingly, the epithelium-specific hnRNPI knockout neonates contain aberrantly high IRAK1 protein levels in the colons and fail to develop immune tolerance to environmental microbes. Our results demonstrate that hnRNPI plays a critical role in establishing neonatal immune adaptation and preventing colitis and colorectal cancer.
authors.affiliation: Department of comparative Biosciences, College of veterinary medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.
authors.forename: Zhigang
authors.identifier: 0000-0001-7557-2968
authors.initials: Z
authors.lastname: Jin
authors.affiliation: Department of statistics, University of Illinois at Urbana-Champaign, Champaign, Illinois, United States of America.
authors.forename: Feng
authors.initials: F
authors.lastname: Liang
authors.affiliation: Department of comparative Biosciences, College of veterinary medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.
authors.forename: Jing
authors.identifier: 0000-0002-4983-1660
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of comparative Biosciences, College of veterinary medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.
authors.forename: Wenyan
authors.identifier: 0000-0001-5270-7727
authors.initials: W
authors.lastname: Mei
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics*; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D003092:Colitis / Q000235:genetics* / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics* / Q000378:metabolism; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D053592:Interleukin-1 Receptor-Associated Kinases / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D038941:Polypyrimidine Tract-Binding Protein / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D034441:Heterogeneous-Nuclear Ribonucleoproteins; D016328:NF-kappa B; C573992:Ptbp1 protein, mouse; D038941:Polypyrimidine Tract-Binding Protein; D053592:Interleukin-1 Receptor-Associated Kinases; C507769:Irak1 protein, mouse