Roles for T/B lymphocytes and ILC2s in experimental chronic obstructive pulmonary disease

Abstract

Pulmonary inflammation in chronic obstructive pulmonary disease (COPD) is characterized by both innate and adaptive immune responses; however, their specific roles in the pathogenesis of COPD are unclear. Therefore, we investigated the roles of T and B lymphocytes and group 2 innate lymphoid cells (ILC2s) in airway inflammation and remodelling, and lung function in an experimental model of COPD using mice that specifically lack these cells (Rag1−/− and Rorafl/flIl7rCre [ILC2‐deficient] mice). Wild‐type (WT) C57BL/6 mice, Rag1−/−, and Rorafl/flIl7rCre mice were exposed to cigarette smoke (CS; 12 cigarettes twice a day, 5 days a week) for up to 12 weeks, and airway inflammation, airway remodelling (collagen deposition and alveolar enlargement), and lung function were assessed. WT, Rag1−/−, and ILC2‐deficient mice exposed to CS had similar levels of airway inflammation and impaired lung function. CS exposure increased small airway collagen deposition in WT mice. Rag1−/− normal air‐ and CS‐exposed mice had significantly increased collagen deposition compared to similarly exposed WT mice, which was associated with increases in IL‐33, IL‐13, and ILC2 numbers. CS‐exposed Rorafl/flIl7rCre mice were protected from emphysema, but had increased IL‐33/IL‐13 expression and collagen deposition compared to WT CS‐exposed mice. T/B lymphocytes and ILC2s play roles in airway collagen deposition/fibrosis, but not inflammation, in experimental COPD.

Enhancing tristetraprolin activity reduces the severity of cigarette smoke‐induced experimental chronic obstructive pulmonary disease

“…[18][19][20][21][22][23] As expected, chronic CS exposure of wild-type mice increased collagen deposition around the airways compared to normal air-exposed wild-type controls (Figure 3a). [18][19][20][21][22][23] As expected, chronic CS exposure of wild-type mice increased collagen deposition around the airways compared to normal air-exposed wild-type controls (Figure 3a).…”

“…We previously showed that mice develop small airway remodelling characterised by increases in collagen deposition, epithelial cell area and numbers of nuclei around and in the small airways in experimental COPD. [18][19][20][21][22][23] As expected, chronic CS exposure of wild-type mice increased collagen deposition around the airways compared to normal air-exposed wild-type controls (Figure 3a). CS-exposed Zfp36 aa/aa mice were protected against collagen deposition with no differences compared to normal air-exposed Zfp36 aa/aa controls and had significantly reduced deposition compared to CS-exposed wild-type controls.…”

“…18,19,21,23,24,50,51 In our current study, Zfp36 aa/aa mice were protected against CS-induced alveolar enlargement. 18,19,21,23,24,50,51 In our current study, Zfp36 aa/aa mice were protected against CS-induced alveolar enlargement.…”

“…[18][19][20][21][22][23][24] In this study, chronic CS exposure of wild-type mice for 8 weeks resulted in increased alveolar diameter and septal damage, which were assessed using the mean linear intercept and destructive index methods, respectively, compared to air-exposed wild-type controls ( Figure 3b). [18][19][20][21][22][23][24] In this study, chronic CS exposure of wild-type mice for 8 weeks resulted in increased alveolar diameter and septal damage, which were assessed using the mean linear intercept and destructive index methods, respectively, compared to air-exposed wild-type controls ( Figure 3b).…”

“…[18][19][20][21][22][23][24]30,50,51,[68][69][70] Exposures are equivalent to a pack-aday smoker. [18][19][20][21][22][23][24]30,50,51,[68][69][70] Exposures are equivalent to a pack-aday smoker.…”