Acute Colitis Drives Tolerance by Persistently Altering the Epithelial Barrier and Innate and Adaptive Immunity

Inflammatory Bowel Diseases
Hannah R WardillPatrick A Hughes

Abstract

Inflammatory bowel disease (IBD) has a remitting and relapsing disease course; however, relatively little is understood regarding how inflammatory damage in acute colitis influences the microbiota, epithelial barrier, and immune function in subsequent colitis. Mice were administered trinitrobenzene sulphonic acid (TNBS) via enema, and inflammation was assessed 2 days (d2) or 28 days (d28) later. Colitis was reactivated in some mice by re-treating at 28 days with TNBS and assessing 2 days later (d30). Epithelial responsiveness to secretagogues, microbiota composition, colonic infiltration, and immune activation was compared between all groups. At day 28, the distal colon had healed, mucosa was restored, and innate immune response had subsided, but colonic transepithelial transport (P = 0.048), regulatory T-cell (TREG) infiltration (P = 0.014), adherent microbiota composition (P = 0.0081), and responsiveness of stimulated innate immune bone marrow cells (P < 0.0001 for IL-1β) differed relative to health. Two days after subsequent instillation of TNBS (d30 mice), the effects on inflammatory damage (P < 0.0001), paracellular permeability (P < 0.0001), and innate immune infiltration (P < 0.0001 for Ly6C+ Ly6G- macrophages) were redu...Continue Reading

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Citations

Nov 25, 2020·Scientific Reports·Nicole DmochowskaPatrick A Hughes
Mar 6, 2021·Indian Journal of Gastroenterology : Official Journal of the Indian Society of Gastroenterology·Janine S Y TamJoanne M Bowen
Mar 28, 2021·Inflammatory Bowel Diseases·Jian FangXiaohong Zhang

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