Recirculating Immunocompetent Cells in Colitic Mice Intensify Their Lung Response to Bacterial Endotoxin

Ahmed Metwali, Peter S. Thorne, M. Nedim Ince, Nervana Metwali, Sarah Winckler, Xiaoqun Guan, Sonay Beyatli, Jamie Truscott, Joseph F. Urban, David E. Elliott

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Patients with inflammatory bowel disease have higher incidence of airway hyperresponsiveness compared to the general population. Lung inflammation leading to airway hyperresponsiveness causes illnesses for more than ten percent of the population in USA. Aims: We investigated the lung response to bacterial endotoxin in colitic mice. Methods: Rag-1 mice were transplanted with negatively selected splenic T cells. Some mice groups were treated with NSAID to develop colitis. All mice were treated with bacterial endotoxin and necropsied 3 weeks later. Results: Colitic mice developed intensified lung inflammation on day 21 of treatment with bacterial endotoxin. Pulmonary lymphocytes from colitic mice displayed a proinflammatory cytokine profile, expressed high ICAM1 and low FoxP3. CD11c + , CD8 + cells bound and responded to non-systemic antigens from gut-localized microbiota and had higher expression of TLR4. Conclusions: Colitic mice developed exacerbated lung inflammation in response to bacterial endotoxin compared to non-colitic mice. Proinflammatory cytokines from pulmonary lymphocytes induced high expression of ICAM1 and suppressed FoxP3 on CD4 + cells. CD11c + , CD8 + cells binding and responding to gut-localized antigens as well as high expression of TLR4 indicate innate and adaptive lung response to bacterial endotoxin. Inflammatory cells from colons of colitic mice homed in the lungs as well as the intestine suggesting recirculation of sensitized immunocompetent cells. These data support our hypothesis that colitis intensifies lung inflammation.

Original languageEnglish (US)
Pages (from-to)2930-2939
Number of pages10
JournalDigestive Diseases and Sciences
Volume63
Issue number11
DOIs
StatePublished - Nov 1 2018
Externally publishedYes

Keywords

  • Airway hyperresponsiveness
  • Bacterial endotoxin
  • Effector and regulatory cells
  • Inflammatory bowel disease (IBD)
  • Innate and adaptive immune responses
  • Lymphocyte recirculation

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology

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