Differential effects of smoking and COPD upon circulating myeloid derived suppressor cells

Summary Background Chronic obstructive pulmonary disease (COPD) is characterized by an enhanced and persistent innate and acquired immune response to tobacco smoking. Myeloid-derived suppressor cells (MDSCs) modulate T-cell responses by down-modulating the T cell receptor ζ chain (TCR ζ) through the...

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Bibliographic Details
Published in:Respiratory medicine 2013-12, Vol.107 (12), p.1895-1903
Main Authors: Scrimini, Sergio, Pons, Jaume, Agustí, Alvar, Soriano, Joan B, Cosio, Borja G, Torrecilla, Juan A, Núñez, Belén, Córdova, Rocío, Iglesias, Amanda, Jahn, Andreas, Crespi, Catalina, Sauleda, Jaume
Format: Article
Language:English
Subjects:
Arginase - metabolism
Arginase I
Blood
Case-Control Studies
CD4-Positive T-Lymphocytes - immunology
CD4-Positive T-Lymphocytes - metabolism
CD8-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - metabolism
Chronic inflammation
Chronic obstructive pulmonary disease
Disease
Down-Regulation - immunology
Female
Forced Expiratory Volume - physiology
Humans
Immune system
Immunity, Cellular - immunology
Immunology
Lymphocytes
Male
Middle Aged
Myeloid cells
Myeloid Cells - immunology
Myeloid Cells - metabolism
Pulmonary Disease, Chronic Obstructive - immunology
Pulmonary/Respiratory
Receptors, Antigen, T-Cell, alpha-beta - immunology
Receptors, Antigen, T-Cell, alpha-beta - metabolism
Smoking
Smoking - immunology
T cell receptors
T-cell receptor ζ chain
Up-Regulation - immunology
Vital Capacity - physiology
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Summary:Summary Background Chronic obstructive pulmonary disease (COPD) is characterized by an enhanced and persistent innate and acquired immune response to tobacco smoking. Myeloid-derived suppressor cells (MDSCs) modulate T-cell responses by down-modulating the T cell receptor ζ chain (TCR ζ) through the catabolism of l -arginine. The effects of smoking on MDSCs and their potential participation in COPD immunopathogenesis have not been explored so far. Methods To investigate it, we compared the level of circulating Lineage-/HLA-DR-/CD33+/CD11b+ MDSCs, the serum concentration of arginase I (ARG I) and the expression of peripheral T-cell receptor ζ chain (TCR ζ) in never smokers, smokers with normal spirometry and COPD patients. Flow cytometry was used to quantify circulating MDSCs and TCR ζ expression. Serum ARG I levels were determined by ELISA. Results The main findings of this study were that: (1) current smoking upregulates and activates circulating MDSCs both in smoker controls and COPD patients; and, (2) at variance with the smokers with normal spirometry, in patients with COPD this effect persists after quitting smoking and is accompanied by a significant and specific down-regulation of the TCR ζ chain expression in circulating T lymphocytes. Conclusion Smoking modulates circulating MDSCs. Their regulation appears altered in patients with COPD.
ISSN:0954-6111
1532-3064
DOI:10.1016/j.rmed.2013.08.002