Recirculating Immunocompetent Cells in Colitic Mice Intensify Their Lung Response to Bacterial Endotoxin
- Resource Type
- Authors
- Peter S. Thorne; M. Nedim Ince; Jamie Truscott; Sarah Winckler; Sonay Beyatli; Nervana Metwali; David E. Elliott; Xiaoqun Guan; Ahmed Metwali; Joseph F. Urban
- Source
- Digestive Diseases and Sciences
- Subject
- 0301 basic medicine
Effector and regulatory cells
Physiology
Lymphocyte recirculation
Population
Inflammation
Inflammatory bowel disease
Proinflammatory cytokine
03 medical and health sciences
Airway hyperresponsiveness
Antigen
Cell Movement
Helminths
Respiratory Hypersensitivity
medicine
Animals
Lymphocytes
Colitis
education
Lung
education.field_of_study
business.industry
Bacterial endotoxin
Gastroenterology
Innate and adaptive immune responses
FOXP3
Forkhead Transcription Factors
Intercellular Adhesion Molecule-1
medicine.disease
3. Good health
Endotoxins
Mice, Inbred C57BL
Toll-Like Receptor 4
030104 developmental biology
medicine.anatomical_structure
Inflammatory bowel disease (IBD)
Immunology
Cytokines
Female
Original Article
medicine.symptom
business
- Language
- ISSN
- 1573-2568
0163-2116
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.