Acute colitis drives tolerance by persistently altering the epithelial barrier and innate and adaptive immunity

Hannah R. Wardill, Jocelyn Choo, Nicole Dmochowska, Chris Mavrangelos, Melissa A. Campaniello, Joanne M. Bowen, Geraint Rogers, Patrick A. Hughes

Research output: Contribution to journalArticle

Abstract

Background: 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. Methods: 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. Results: 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 reduced relative to d2 colitis. However, TREG infiltration was increased (P < 0.0001), and the responsiveness of stimulated T cells in the mesenteric lymph nodes shifted from pro-inflammatory at d2 to immune-suppressive at d30 (P < 0.0001 for IL-10). These effects were observed despite similar colonic microbiota composition and degradation of the mucosal layer between d2 and d30. Conclusions: Collectively, these results indicate that acute colitis chronically alters epithelial barrier function and both innate and adaptive immune responses. These effects reduce the consequences of a subsequent colitis event, warranting longitudinal studies in human IBD subjects.

LanguageEnglish
Pages1196-1207
Number of pages12
JournalInflammatory Bowel Diseases
Volume25
Issue number7
DOIs
Publication statusPublished - 18 Jun 2019

Keywords

  • Epithelial barrier
  • Immune tolerance
  • Inflammatory bowel disease
  • Microbiota

ASJC Scopus subject areas

  • Immunology and Allergy
  • Gastroenterology

Cite this

Wardill, H. R., Choo, J., Dmochowska, N., Mavrangelos, C., Campaniello, M. A., Bowen, J. M., ... Hughes, P. A. (2019). Acute colitis drives tolerance by persistently altering the epithelial barrier and innate and adaptive immunity. Inflammatory Bowel Diseases, 25(7), 1196-1207. https://doi.org/10.1093/ibd/izz011
Wardill, Hannah R. ; Choo, Jocelyn ; Dmochowska, Nicole ; Mavrangelos, Chris ; Campaniello, Melissa A. ; Bowen, Joanne M. ; Rogers, Geraint ; Hughes, Patrick A. / Acute colitis drives tolerance by persistently altering the epithelial barrier and innate and adaptive immunity. In: Inflammatory Bowel Diseases. 2019 ; Vol. 25, No. 7. pp. 1196-1207.
@article{a59a67116d2646688808aaaf07fc1b1a,
title = "Acute colitis drives tolerance by persistently altering the epithelial barrier and innate and adaptive immunity",
abstract = "Background: 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. Methods: 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. Results: 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 reduced relative to d2 colitis. However, TREG infiltration was increased (P < 0.0001), and the responsiveness of stimulated T cells in the mesenteric lymph nodes shifted from pro-inflammatory at d2 to immune-suppressive at d30 (P < 0.0001 for IL-10). These effects were observed despite similar colonic microbiota composition and degradation of the mucosal layer between d2 and d30. Conclusions: Collectively, these results indicate that acute colitis chronically alters epithelial barrier function and both innate and adaptive immune responses. These effects reduce the consequences of a subsequent colitis event, warranting longitudinal studies in human IBD subjects.",
keywords = "Epithelial barrier, Immune tolerance, Inflammatory bowel disease, Microbiota",
author = "Wardill, {Hannah R.} and Jocelyn Choo and Nicole Dmochowska and Chris Mavrangelos and Campaniello, {Melissa A.} and Bowen, {Joanne M.} and Geraint Rogers and Hughes, {Patrick A.}",
year = "2019",
month = "6",
day = "18",
doi = "10.1093/ibd/izz011",
language = "English",
volume = "25",
pages = "1196--1207",
journal = "Inflammatory Bowel Diseases",
issn = "1078-0998",
publisher = "John Wiley and Sons Inc.",
number = "7",

}

Acute colitis drives tolerance by persistently altering the epithelial barrier and innate and adaptive immunity. / Wardill, Hannah R.; Choo, Jocelyn; Dmochowska, Nicole; Mavrangelos, Chris; Campaniello, Melissa A.; Bowen, Joanne M.; Rogers, Geraint; Hughes, Patrick A.

In: Inflammatory Bowel Diseases, Vol. 25, No. 7, 18.06.2019, p. 1196-1207.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Acute colitis drives tolerance by persistently altering the epithelial barrier and innate and adaptive immunity

AU - Wardill, Hannah R.

AU - Choo, Jocelyn

AU - Dmochowska, Nicole

AU - Mavrangelos, Chris

AU - Campaniello, Melissa A.

AU - Bowen, Joanne M.

AU - Rogers, Geraint

AU - Hughes, Patrick A.

PY - 2019/6/18

Y1 - 2019/6/18

N2 - Background: 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. Methods: 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. Results: 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 reduced relative to d2 colitis. However, TREG infiltration was increased (P < 0.0001), and the responsiveness of stimulated T cells in the mesenteric lymph nodes shifted from pro-inflammatory at d2 to immune-suppressive at d30 (P < 0.0001 for IL-10). These effects were observed despite similar colonic microbiota composition and degradation of the mucosal layer between d2 and d30. Conclusions: Collectively, these results indicate that acute colitis chronically alters epithelial barrier function and both innate and adaptive immune responses. These effects reduce the consequences of a subsequent colitis event, warranting longitudinal studies in human IBD subjects.

AB - Background: 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. Methods: 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. Results: 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 reduced relative to d2 colitis. However, TREG infiltration was increased (P < 0.0001), and the responsiveness of stimulated T cells in the mesenteric lymph nodes shifted from pro-inflammatory at d2 to immune-suppressive at d30 (P < 0.0001 for IL-10). These effects were observed despite similar colonic microbiota composition and degradation of the mucosal layer between d2 and d30. Conclusions: Collectively, these results indicate that acute colitis chronically alters epithelial barrier function and both innate and adaptive immune responses. These effects reduce the consequences of a subsequent colitis event, warranting longitudinal studies in human IBD subjects.

KW - Epithelial barrier

KW - Immune tolerance

KW - Inflammatory bowel disease

KW - Microbiota

UR - http://www.scopus.com/inward/record.url?scp=85068401751&partnerID=8YFLogxK

U2 - 10.1093/ibd/izz011

DO - 10.1093/ibd/izz011

M3 - Article

VL - 25

SP - 1196

EP - 1207

JO - Inflammatory Bowel Diseases

T2 - Inflammatory Bowel Diseases

JF - Inflammatory Bowel Diseases

SN - 1078-0998

IS - 7

ER -