Dendritic cells induce Tc1 cell differentiation via the CD40/CD40L pathway in mice after exposure to cigarette smoke.

Abstract

Dendritic cells and CD8(+) T cells participate in the pathology of chronic obstructive pulmonary disease, including emphysema, but little is known of the involvement of the CD40/CD40L pathway. We investigated the role of the CD40/CD40L pathway in Tc1 cell differentiation induced by dendritic cells in a mouse model of emphysema, and in vitro. C57BL/6J wild-type and CD40(-/-) mice were exposed to cigarette smoke (CS) or not (control), for 24 wk. In vitro experiments involved wild-type and CD40(-/-) dendritic cells treated with CS extract (CSE) or not. Compared with the control groups, the CS mice (both wild type and CD40(-/-)) had a greater percentage of lung dendritic cells and higher levels of major histocompatability complex (MHC) class I molecules and costimulatory molecules CD40 and CD80. Relative to the CS CD40(-/-) mice, the CS wild type showed greater signs of lung damage and Tc1 cell differentiation. In vitro, the CSE-treated wild-type cells evidenced more cytokine release (IL-12/p70) and Tc1 cell differentiation than did the CSE-treated CD40(-/-) cells. Exposure to cigarette smoke increases the percentage of lung dendritic cells and promotes Tc1 cell differentiation via the CD40/CD40L pathway. Blocking the CD40/CD40L pathway may suppress development of emphysema in mice exposed to cigarette smoke.

• Authors: Liang-Jian Kuang, Ting-Ting Deng, Qin Wang, Shi-Lin Qiu, Yi Liang, Zhi-Yi He, Jian-Quan Zhang, Jing Bai, Mei-Hua Li, Jing-Min Deng, Guang-Nan Liu, Ji-Feng Liu, Xiao-Ning Zhong
• Journal: American journal of physiology. Lung cellular and molecular physiology (Am J Physiol Lung Cell Mol Physiol) Vol. 311 Issue 3 Pg. L581-9 (09 01 2016) ISSN: 1522-1504 [Electronic] United States
• PMID: 27448664 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 the American Physiological Society.

Chemical References

• CD40 Antigens
• Cytokines
• Smoke
• T-Box Domain Proteins
• T-box transcription factor TBX21
• CD40 Ligand

Topics

• Animals
• CD40 Antigens (physiology)
• CD40 Ligand (physiology)
• CD8-Positive T-Lymphocytes
• Cell Differentiation
• Cells, Cultured
• Cytokines (biosynthesis, genetics)
• Dendritic Cells (physiology)
• Lung (immunology, metabolism, pathology)
• Lymphocyte Count
• Mice, Inbred C57BL
• Mice, Knockout
• Pulmonary Emphysema (etiology, immunology, metabolism)
• Signal Transduction
• Smoke (adverse effects)
• Smoking (adverse effects)
• T-Box Domain Proteins (genetics, metabolism)
• Tobacco (adverse effects)