CD39/CD73 and the imbalance of Th17 cells and regulatory T cells in allergic asthma.
In the immune system, CD4+CD25+Foxp3+ regulatory T cells (Tregs) maintain self‑tolerance and Th17 cells mediate inflammatory responses. CD39 is expressed on the surface of a subset of naturally occurring human Tregs that are important in constraining pathogenic Th17 cells. Additional studies have shown that Tregs differentiate into interleukin‑17 (IL‑17)+Foxp3+ T cells. Our previous study indicated an imbalance of Th17 and Tregs in allergic asthma; however, the underlying mechanisms remain poorly understood. Using quantitative PCR (qPCR), CD39 and CD73 mRNA levels in CD4+ T cells were investigated. Flow cytometry was used to analyze the proportion of IL‑17+Foxp3+ T cells, and CD39 and CD73 expressed by CD4+ T cells and Tregs in the peripheral blood of the subjects. The results of the present study demonstrated an increased frequency of CD4+Foxp3+IL‑17+ T cells in moderate to severe asthma. A deficiency in CD39 expressed on the surface of CD4+ T cells and Tregs was observed in asthma patients. The expression of CD39 and CD73 on the surface of CD4+ T cells and Tregs was negatively correlated with the number of Th17 cells. These results indicated that the plasticity of Tregs transforming to IL‑17+Foxp3+CD4+ T cells, the reduced frequency of CD39+ Tregs and less effective suppression of IL‑17 production by residual CD39+ Tregs leads to an imbalance of Th17 and Tregs in asthma. Therefore, enhanced CD39 activity is hypothesized to prevent the progression of asthma.
Department of Pulmonary Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.
Lin-Lin
LL
Wang
Hua-Ping
HP
Tang
Guo-Chao
GC
Shi
Huan-Ying
HY
Wan
Wei
W
Tang
Xiao-Xia
XX
Hou
Li-Na
LN
Pan
Bao-Yu
BY
Shi
Lian-Qin
LQ
Tao
D015720:5'-Nucleotidase / Q000276:immunology* / Q000378:metabolism; D000328:Adult; D015703:Antigens, CD / Q000276:immunology* / Q000378:metabolism; D001081:Apyrase / Q000276:immunology* / Q000378:metabolism; D001249:Asthma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016022:Case-Control Studies; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D058851:GPI-Linked Proteins / Q000276:immunology / Q000378:metabolism; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology* / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism
D015703:Antigens, CD; D058851:GPI-Linked Proteins; D020381:Interleukin-17; D012333:RNA, Messenger; D015720:5'-Nucleotidase; C548241:NT5E protein, human; D001081:Apyrase; C067869:CD39 antigen