Generation and Immune Regulation of CD4+CD25−Foxp3+ T Cells in Chronic Obstructive Pulmonary Disease
| Autor: | Yang Jin, Xiaonan Tao, Shuai-Ying Miao, Zhao-Ji Meng, Hong-Li Han, Jiang-Hua Wu, Xian-Zhi Xiong, Mei Zhou, Sheng-Wen Sun |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
lcsh:Immunologic diseases. Allergy T cell Immunology Inflammation chemical and pharmacologic phenomena CD4+CD25−Foxp3+ T cells Flow cytometry 03 medical and health sciences immune dysfunction 0302 clinical medicine Immune system TIGIT medicine Immunology and Allergy COPD IL-2 receptor Th17 cells Interleukin-7 receptor medicine.diagnostic_test Chemistry FOXP3 hemic and immune systems Molecular biology 030104 developmental biology medicine.anatomical_structure CD4+CD25+Foxp3+ T cells medicine.symptom lcsh:RC581-607 030215 immunology |
| Zdroj: | Frontiers in Immunology, Vol 10 (2019) |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2019.00220/full |
| Popis: | The imbalance of CD4+Foxp3+ T cell subsets is reportedly involved in abnormal inflammatory immune responses in patients with chronic obstructive pulmonary disease (COPD). However, the possible role of CD4+CD25-Foxp3+ T cells in immune regulation in COPD remains to be investigated. In the current study, distribution and phenotypic characteristics of CD4+CD25-Foxp3+ T cells from peripheral blood were determined by flow cytometry; the origin, immune function and ultimate fate of CD4+CD25-Foxp3+ T cells were further explored in vitro. It was observed that circulating CD4+CD25-Foxp3+ T cells were significantly increased in stable COPD patients (SCOPD) and resembled central memory or effector memory T cells. Compared with peripheral CD4+CD25+Foxp3+ T cells, peripheral CD4+CD25-Foxp3+ T cells showed a lower expression of Foxp3, CTLA-4, HELIOS, and TIGIT, but a higher expression of CD127 and KI-67, suggesting that CD4+CD25-Foxp3+ T cells lost the expression of Tregs-associated molecules following the reduction in CD25. Unexpectedly, our study found that transforming growth factor-β1 (TGFβ1) decreased CD25 expression and played a critical role in the generation of CD4+CD25-Foxp3+ T cells from CD4+CD25+Foxp3+ T cells. Phenotypic analysis further revealed that both inducible and peripheral CD4+CD25-Foxp3+ T cells exhibited the features of activated conventional T cells. Importantly, memory CD4+CD25-Foxp3+ T cells facilitated the proliferation and differentiation of naive CD4+ T cells into Th17 cells in the presence of IL-1β, IL-6, IL-23, and TGFβ1. Finally, a fraction of CD4+CD25-Foxp3+ T cells, exhibiting instability and plasticity, were converted to Th17 cells when subjected to Th17 cell-polarizing condition. Taken together, we propose that TGFβ1 is responsible for the generation of CD4+CD25-Foxp3+ T cells, and these cells functionally exert an auxiliary effect on Th17 cells generation and might perpetuate chronic inflammation in COPD. |
| Databáze: | OpenAIRE |
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