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

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.

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.

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 simultaneously secrete IFN-γ, TNF-α 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.

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.