Location: Animal Parasitic Diseases LaboratoryTitle: Mechanisms of exacerbating lung inflammation in inflammatory bowel disease
|METWALI, AHMED - University Of Iowa|
|THORNE, PETER - University Of Iowa|
|WINCKLER, SARAH - University Of Iowa|
|METWALI, NERVANA - University Of Iowa|
|ELLIOTT, DAVID - University Of Iowa|
|INCE, MN - University Of Iowa|
|GUAN, X - University Of Iowa|
|BEYATLI, S - University Of Iowa|
|TRUSCOTT, J - University Of Iowa|
Submitted to: Digestive Disease and Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/3/2018
Publication Date: 7/11/2018
Citation: Metwali, A., Thorne, P., Winckler, S., Metwali, N., Urban Jr, J.F., Elliott, D.E., Ince, M., Guan, X., Beyatli, S., Truscott, J. 2018. Mechanisms of exacerbating lung inflammation in inflammatory bowel disease. Digestive Disease and Science. https://doi.org/10.1007/s10620-018-5196-z.
Interpretive Summary: People with inflammatory bowel disease of the intestine have increased prevalence of asthma in the lungs. The tissues of the intestinal colon and lungs have similarities that support the same disease state at both sites. It has been considered that the recruitment of activated effector cells released from the intestine into the blood can ultimately cause damage to tissue sites in the lung and elsewhere. This may be due to homing receptors on cells activated in the intestine that then settle in other sites. Scientists from the University of Iowa and USDA/ARS in Beltsville identified cell effector, regulatory and adhesion molecules that were activated in the intestinal compartment of mice with colitis. A parasite model was also used to show that worm infection of the intestine activate cells responsive to parasite molecules that then relocate to the lungs where they respond with a pattern indicative of that to the worm in the intestine. This information is important to researchers that want to understand how parasites modulate responses at other tissue sites and how these response can be regulated to reduce disease.
Technical Abstract: A mouse model of lung inflammation secondary to colitis was developed to study mechanisms of the accelerated lung inflammation in response to challenge with bacterial endotoxin. Colitic mice developed accelerated lung inflammation compared to non-colitic mice with the same treatment. The cytokine pattern of the lung lymphocytes replicated that from the intestinal lamina propria lymphocytes (LPL). Pulmonary CD4+ lymphocytes from colitic mice displayed a pro-inflammatory cytokine profile as more IFN'+ and fewer IL-10+ cells were found. Lower expression of FoxP3 regulatory marker and higher ICAM1 pro-inflammatory marker existed in colitic compared to lung lymphocytes from non-colitic mice with the same treatment. This is the first report demonstrating suppressed expression of a4ß7 on non-regulatory IEC and LPL from colitic mice. This deranged expression highlighted the possibility of homing of these cells to other organs. The presence of CD11c+ cells with high expression of TLR4 and capable of binding gut antigens in the lungs of colitic mice favored the accelerated inflammatory response to bacterial endotoxin and raises the possibility of gut antigens carry-over with dendritic cells migrating from the intestine to the lungs. Taken together, these findings support our hypothesis that chronic intestinal inflammation exacerbates asthma.