Γδ T cells protect against LPS-induced lung injury. Issue 2 (1st October 2015)

• Record Type: Journal Article
• Authors: Wehrmann, Fabian; Lavelle, James C; Collins, Colm B; Tinega, Alex N; Thurman, Joshua M; Burnham, Ellen L; Simonian, Philip L
• Is Part Of: Journal of leukocyte biology. Volume 99:Issue 2(2016)
• Page Start: 373
• Page End: 386
• Publication Date: 2015-10-01
• Subjects: macrophages -- IL-4 -- ARDS -- alveolar-capillary leak -- TNF-α; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1189/jlb.4A0115-017RR
• Languages: English
• ISSNs: 0741-5400

Abstract

Abstract : IL4-expressing γδ T cells decrease TNF-α production by alveolar macrophages, reducing accumulation of M1 macrophages that promotes lung injury. Abstract: γδ T lymphocytes are a unique T cell population with important anti-inflammatory capabilities. Their role in acute lung injury, however, is poorly understood but may provide significant insight into lung-protective mechanisms occurring after injury. In a murine model of lung injury, wild-type C57BL/6 and TCRδ −/− mice were exposed to Escherichia coli LPS, followed by analysis of γδ T cell and macrophage subsets. In the absence of γδ T cells, TCRδ −/− mice developed increased inflammation and alveolar-capillary leak compared with wild-type C57BL/6 mice after LPS exposure that correlated with expansion of distinct macrophage populations. Classically activated M1 macrophages were increased in the lung of TCRδ −/− mice at d 1, 4, and 7 after LPS exposure that peaked at d 4 and persisted at d 7 compared with wild-type animals. In response to LPS, Vγ1 and Vγ7 γδ T cells were expanded in the lung and expressed IL-4 . Coculture experiments showed decreased expression of TNF-α by resident alveolar macrophages in the presence of γδ T cells that was reversed in the presence of an anti-IL-4-blocking antibody. Treatment of mice with rIL4 resulted in reduced numbers of M1 macrophages, inflammation, and alveolar-capillary leak. Therefore, one mechanism by which Vγ1 and Vγ7 γδ T cells protect against LPS-induced lung injury is through IL-4 expression, which decreases TNF-α production by resident alveolar macrophages, thus reducing accumulation of M1 macrophages, inflammation, and alveolar-capillary leak.