Soluble common gamma chain exacerbates COPD progress through the regulation of inflammatory T cell response in mice

Byunghyuk Lee; Eunhee Ko; Jiyeon Lee; Yuna Jo; Hyunju Hwang; Tae Sik Goh; Myungsoo Joo; Changwan Hong

doi:10.2147/COPD.S123405

Soluble common gamma chain exacerbates COPD progress through the regulation of inflammatory T cell response in mice

Int J Chron Obstruct Pulmon Dis. 2017 Mar 8:12:817-827. doi: 10.2147/COPD.S123405. eCollection 2017.

Authors

Byunghyuk Lee¹, Eunhee Ko¹, Jiyeon Lee², Yuna Jo¹, Hyunju Hwang¹, Tae Sik Goh³, Myungsoo Joo², Changwan Hong¹

Affiliations

¹ Department of Anatomy and Cell Biology, Pusan National University School of Medicine.
² Division of Applied Medicine, School of Korean Medicine, Pusan National University, Yangsan.
³ Department of Anatomy and Cell Biology, Pusan National University School of Medicine; Department of Orthopedic Surgery, Medical Research Institute, Pusan National University School of Medicine, Busan, South Korea.

Abstract

Cigarette smoking (CS) is a major cause of considerable morbidity and mortality by inducing lung cancer and COPD. COPD, a smoking-related disorder, is closely related to the alteration of immune system and inflammatory processes that are specifically mediated by T cells. Soluble common gamma chain (sγc) has recently been identified as a critical regulator of the development and differentiation of T cells. We examined the effects of sγc in a cigarette smoke extract (CSE) mouse model. The sγc level in CSE mice serum is significantly downregulated, and the cellularity of lymph node (LN) is systemically reduced in the CSE group. Overexpression of sγc enhances the cellularity and IFNγ production of CD8 T cells in LN and also enhances Th1 and Th17 differentiation of CD4 T cells in the respiratory tract. Mechanistically, the downregulation of sγc expression mediated by CSE is required to prevent excessive inflammatory T cell responses. Therefore, our data suggest that sγc may be one of the target molecules for the control of immunopathogenic progresses in COPD.

Keywords: COPD; T cell; cytokine; soluble common gamma chain.

MeSH terms

Animals
CD8-Positive T-Lymphocytes / immunology
CD8-Positive T-Lymphocytes / metabolism
Disease Models, Animal
Disease Progression
Interferon-gamma / immunology
Interferon-gamma / metabolism
Interleukin Receptor Common gamma Subunit / genetics
Interleukin Receptor Common gamma Subunit / immunology*
Interleukin Receptor Common gamma Subunit / metabolism
Lung / immunology*
Lung / pathology
Lymph Nodes / immunology
Lymph Nodes / metabolism
Mice, Inbred C57BL
Mice, Transgenic
Pneumonia / etiology
Pneumonia / genetics
Pneumonia / immunology*
Pneumonia / metabolism
Pulmonary Disease, Chronic Obstructive / etiology
Pulmonary Disease, Chronic Obstructive / genetics
Pulmonary Disease, Chronic Obstructive / immunology*
Pulmonary Disease, Chronic Obstructive / metabolism
Signal Transduction
Smoke / adverse effects
Smoking / adverse effects
T-Lymphocyte Subsets / immunology*
T-Lymphocyte Subsets / metabolism
Th1 Cells / immunology
Th1 Cells / metabolism
Th17 Cells / immunology
Th17 Cells / metabolism
Time Factors

Substances

IFNG protein, mouse
Il2rg protein, mouse
Interleukin Receptor Common gamma Subunit
Smoke
Interferon-gamma