Premium
The T helper type 17/regulatory T cell imbalance was associated with Ras‐ GTP ase overexpression in patients with pulmonary hypertension associated with chronic obstructive pulmonary disease
Author(s) -
Zhu Rong,
Xie Xiaochen,
Wang Nana,
Chen Liang,
Hong Yongqing
Publication year - 2019
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.13084
Subject(s) - copd , foxp3 , cd28 , immunology , medicine , endocrinology , t cell , immune system
Summary Pulmonary hypertension ( PH ) is a common but dangerous complication in chronic obstructive pulmonary disease ( COPD ). We hypothesized that dysregulation in the T helper type 17 (Th17) compartment could contribute to the development of COPD ‐associated PH ( COPD ‐ PH ). To investigate this hypothesis, patients with COPD ‐ PH and age‐ and sex‐matched healthy controls were recruited, and their circulating CD 4 + T cells were activated using anti‐ CD 3/ CD 28 antibodies. The frequency of interleukin‐17 ( IL ‐17) ‐secreting cells was significantly higher in COPD ‐ PH patients than in healthy controls. The secretion of IL ‐17 was significantly higher from COPD ‐ PH CD 4 + T cells than from control CD 4 + T cells, whereas the secretion of interferon‐ γ and IL ‐4 was not significantly different. The expression of transforming growth factor‐ β , on the other hand, was significantly higher in healthy controls than in COPD ‐ PH patients. Activated CD 4 + T cells from COPD ‐ PH patients also presented significantly lower forkhead box P3 ( FOXP 3) and higher retinoic acid receptor‐related orphan C2 ( RORC 2) expression than CD 4 + T cells from healthy controls. In both controls and patients, a negative correlation between RORC 2 and FOXP 3 was found, ex vivo and after CD 3/ CD 28 activation. The serum IL ‐6 level was slightly higher in COPD ‐ PH patients than in controls, but the IL ‐6 transcription by monocytes was comparable in COPD ‐ PH patients and controls. Interestingly, CD 4 + T cells from COPD ‐ PH patients presented significantly higher levels of Kirsten rat sarcoma viral oncogene homolog and neuroblastoma RAS viral oncogene homolog than CD 4 + T cells from healthy controls. Inhibiting Ras‐ GTP ases using farnesylthiosalicylic acid significantly reduced the ratio of RORC 2/ FOXP 3 expression in CD 4 + T cells. Overall, we demonstrated that an imbalance of Th17/regulatory T cells was a hallmark of COPD ‐ PH .