Logo image
Back
Recirculating Immunocompetent Cells in Colitic Mice Intensify Their Lung Response to Bacterial Endotoxin
Journal article   Open access   Peer reviewed

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 and David E Elliott
Digestive diseases and sciences, Vol.63(11), pp.2930-2939
2018
DOI: 10.1007/s10620-018-5196-z
PMCID: PMC6182434
PMID: 30022451
url
https://doi.org/10.1007/s10620-018-5196-zView
Published (Version of record) Open Access

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

Details

Metrics

40 Record Views
5 Times Cited - Web of Science
Logo image