Role of CD69 in the pathogenesis of elastase-induced pulmonary inflammation and emphysema

• Published in: Biochemistry and biophysics reports Vol. 7; pp. 400 - 407
• Main Authors: Fujita, Tetsuo, Yoshioka, Kento, Umezawa, Hiroki, Tanaka, Kensuke, Naito, Yusuke, Nakayama, Toshinori, Hatano, Masahiko, Tatsumi, Koichiro, Kasuya, Yoshitoshi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier 01.09.2016
• Subjects: Chronic obstructive pulmonary disease; CD69; Th17; γδ T cell; IL-17
• ISSN: 2405-5808; 2405-5808
• DOI: 10.1016/j.bbrep.2016.07.010

Cluster of differentiation 69 (CD69), known as an early activation marker of lymphocytes, has been demonstrated to regulate inflammatory events in various disease models. Although the increased number of CD69-expressed T lymphocytes in the lungs of patients with chronic obstructive pulmonary disease (COPD) has been reported, a functional role of CD69 in the pathogenesis of COPD remains unknown. To address to this question, CD69-deficient (CD69KO) mice and wild-type (WT) mice were subjected to a mouse model of porcine pancreatic elastase (PPE)-induced pulmonary inflammation and emphysema. In the two genotypes, PPE increased counts of macrophages, neutrophils and lymphocytes in bronchoalveolar lavage fluid (BALF) and induced emphysematous changes in the lung, whereas those two pathological signs were significantly enhanced in CD69KO mice compared to WT mice. Moreover, the PPE-induced levels of IL-17 and IL-6 in BALF were significantly higher in CD69KO mice than in WT mice at the acute inflammatory phase. Immunofluorescent studies showed that IL-17 and IL-6 were predominantly expressed in CD4 and γδ T cells and macrophages, respectively. Concomitant administration of IL-17- and IL-6-neutralizing antibodies significantly attenuated the PPE-induced emphysematous changes in the two genotypes. These findings suggest that CD69 negatively regulates the development of PPE-induced emphysema in part at least through modulating function of IL-17-producing T cells.