Cigarette smoke–induced reduction of C1q promotes emphysema

• DOI: 10.1172/jci.insight.124317
• Publication Date: 2019-05-21T16:28:53Z
• Authors: Xiaoyi Yuan; Cheng-Yen Chang; Ran You; Ming Shan; Bon Hee Gu; Matthew C. Madison; Gretchen Diehl; Sarah Perusich; Li-Zhen Song; Lorraine Cornwell; Roger D. Rossen; Rick Wetsel; Rajapakshe Kimal; Cristian Coarfa; Holger K. Eltzschig; David B. Corry; Farrah Kheradmand
• Keywords: Adult; Emphysema; 0301 basic medicine; Complement C1q; Gene Expression Profiling; Antigen-Presenting Cells; Down-Regulation; Autoimmunity; Cell Differentiation; Coculture Techniques; Cigarette Smoking; 3. Good health; Disease Models, Animal; 03 medical and health sciences; Case-Control Studies; Gene Knockdown Techniques; Immune Tolerance; Animals; Humans; Female; Cells, Cultured; Aged; Cell Proliferation

Alteration of innate immune cells in the lungs can promote loss peripheral tolerance that leads to autoimmune responses cigarette smokers. Development autoimmunity smokers with emphysema is also strongly linked expansion autoreactive T helper (Th) expressing interferon gamma (Th1), and interleukin 17A (Th17). However, mechanisms responsible for enhanced self-recognition reduced smoker remain less clear. Here we show C1q, a component complement protein 1 complex (C1), downregulated lung CD1a+ antigen presenting (APCs) isolated from emphysematous human, mouse APCs after chronic smoke exposure. C1q potentiated function differentiate CD4+ Tregs, while it inhibited Th17 cell development proliferation. Mice deficient were exposed exhibited exaggerated inflammation marked by increased cells, reconstitution Tregs abundance, dampened smoke-induced inflammation, reversed established emphysema. Our findings demonstrate smoke-mediated could play key role tolerance, which be explored treat