Innate immune processes are sufficient for driving silicosis in mice

Journal of Leukocyte Biology

Andrij Holian²  Celine A. Beamer²  Forrest Jessop²  Melanie Trapkus²  Christopher T. Migliaccio²  Dorothy Yuan¹ 

[1] University of Texas Southwestern Medical Center at Dallas, Graduate School of Biomedical Sciences, Southwestern Medical School, Dallas, Texas, USA University of Texas Southwestern Medical Center at Dallas, Graduate School of Biomedical Sciences, Southwestern Medical School, Dallas, Texas, USA University of Texas Southwestern Medical Center at Dallas, Graduate School of Biomedical Sciences, Southwestern Medical School, Dallas, Texas, USA;The University of Montana, Department of Biomedical and Pharmaceutical Sciences, Center for Environmental Health Sciences, Missoula, Montana, USA; and The University of Montana, Department of Biomedical and Pharmaceutical Sciences, Center for Environmental Health Sciences, Missoula, Montana, USA; and The University of Montana, Department of Biomedical and Pharmaceutical Sciences, Center for Environmental Health Sciences, Missoula, Montana, USA; and

关键词: lung;    inflammation;    fibrosis;    lymphocyte;    cytokine;    inflammasome;   

DOI  :  10.1189/jlb.0210108

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

The lung is constantly exposed to potentially pathogenic particles and microorganisms. It has become evident recently that not only innate but also adaptive immune responses to particulates, such as SiO2 entering the respiratory tract, are complex and dynamic events. Although the cellular mechanisms and anatomical consequences involved in the development of silicosis have been studied extensively, they still remain poorly understood. Based on their capacity for immune regulation, lymphocytes may play a key role in the respiratory response to environmental challenge by SiO2. The objective of this study was to characterize the impact of SiO2 exposure on respiratory immune processes, with particular emphasis on evaluating the importance of lymphocytes in the murine silicosis model. Therefore, lymphopenic mice, including NK-deficient, Rag1−/−, or a combination (Rag1−/− NK-depleted), were used and demonstrated that SiO2-induced fibrosis and inflammation can occur independently of T, B, NK T, and NK cells. Studies in Rag1−/− mice suggest further that lymphocytes may participate in the regulation of SiO2-induced inflammation through modulation of the Nalp3 inflammasome. This observation may have clinical relevance in the treatment of inflammatory and fibrotic lung diseases that are refractory or respond suboptimally to current therapeutics.

【 授权许可】

Unknown