Goblet Cell Derived RELM-β Recruits CD4+ T Cells during Infectious Colitis to Promote Protective Intestinal Epithelial Cell Proliferation

摘要: Enterohemorrhagic Escherichia coli and related food waterborne pathogens pose significant threats to human health. These attaching/effacing microbes infect the apical surface of intestinal epithelial cells (IEC), causing severe diarrheal disease. Colonizing luminal helps segregate these from most host inflammatory responses. Based on studies using Citrobacter rodentium, a mouse pathogen, we speculate that hosts rely immune-mediated changes in IEC, including goblet defend against pathogens. include CD4+ T cell-dependent increase IEC proliferation replace infected as well altered production cell-derived mucin Muc2. Another cell mediator, REsistin-Like Molecule (RELM)-β is strongly induced within during C. rodentium infection, was detected stool serum. Despite its dramatic induction, RELM-β’s role defense unclear. Thus, wildtype RELM-β gene deficient mice (Retnlb-/-) were orally with rodentium. While their burdens only modestly elevated, Retnlb-/- suffered increased mortality mucosal ulceration due deep pathogen penetration colonic crypts. Immunostaining for Ki67 BrDU revealed significantly impaired infection-induced hyper-proliferation. Interestingly, exposure did not directly proliferation, rather acted chemoattractant. Correspondingly, showed recruitment colons, along reduced interleukin (IL)-22, multifunctional cytokine proliferation. Enema delivery restored recruitment, concurrently increasing IL-22 levels while reducing pathology. findings demonstrate play an unexpected, yet critical recruiting colon protect enteric part via induction