STAT3 regulation of Mtb-specific T cell function in active pulmonary tuberculosis patients

Background: Tuberculosis (TB) remains one of the most serious infectious diseases in the world. Our aim was to investigate the regulatory role of STAT3 and pSTAT3 in the regulation of T cell immunophenotype and cell function. Methods: Twenty-five active pulmonary tuberculosis (APTB) patients, 18 latent tuberculosis infection (LTBI) patients, and 20 healthy controls (HCs) enrolled in this study. T cell phenotype and expression of STAT3 and pSTAT3 were detected by flow cytometry. Results: Compared with HCs, the expression of pSTAT3 in CD4+ T and CD8+ T cells in peripheral blood of APTB patients was increased, and the expression was higher in pleural effusion. Multifunctional T cells that simulta-neously secrete IFN-gamma, TNF-alpha and IL-17A have higher pSTAT3 expression levels. Mtb-specific T cells from APTB patients had a higher cell frequency of the STAT3+ pSTAT3+ phenotype and a reduced cell frequency of the STAT3+ pSTAT3- phenotype compared with LTBI patients. Mtb-specific T cells with STAT3+ pSTAT3+ phenotype had higher expression of PD-1 and PD-L1, while cells with STAT3+ pSTAT3- phenotype had higher expression of Bcl-2. Conclusions: STAT3 and pSTAT3 in T cells of APTB patients feature in the process of anti-apoptosis and cytokine secretion. At the same time, the higher pSTAT3 may be related to the degree of cell functional exhaustion. The pSTAT3 level of T cells is related to the infection status and may indicate the clinical activity of the disease, which provides a new idea for the clinical identification and treatment of active pulmonary tuberculosis.

Automated summary

This study investigated the regulatory role of STAT3 and pSTAT3 in the T cell immunophenotype and cell function in tuberculosis (TB) patients. The expression of pSTAT3 was increased in CD4+ T and CD8+ T cells in active pulmonary tuberculosis (APTB) patients, and the expression was higher in pleural effusion. Multifunctional T cells with higher pSTAT3 expression levels were found to secrete IFN-gamma, TNF-alpha, and IL-17A. The pSTAT3 levels in Mtb-specific T cells were associated with the infection status and may indicate the clinical activity of the disease.