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

Ruiqi Chen; Meihui Li; Shuang Qin; Hong Lu; Mo Shen; Xiangyang Lin

doi:10.1016/j.intimp.2023.109748

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

Int Immunopharmacol. 2023 Mar:116:109748. doi: 10.1016/j.intimp.2023.109748. Epub 2023 Feb 6.

Authors

Ruiqi Chen¹, Meihui Li¹, Shuang Qin², Hong Lu¹, Mo Shen³, Xiangyang Lin⁴

Affiliations

¹ Department of Clinical Laboratory, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
² Department of Clinical Laboratory, Jinan City People's Hospital, Jinan, Shandong 271100, China.
³ Department of Clinical Laboratory, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China. Electronic address: shenmo601@163.com.
⁴ Department of Clinical Laboratory, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China. Electronic address: linxy1968@126.com.

PMID: 36753982
DOI: 10.1016/j.intimp.2023.109748

Abstract

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 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.

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.

Keywords: Active pulmonary tuberculosis; Mtb-specific T cells; STAT3.

MeSH terms

CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Humans
Latent Tuberculosis*
Mycobacterium tuberculosis*
STAT3 Transcription Factor
Tuberculosis*
Tuberculosis, Pulmonary*

Substances

STAT3 protein, human
STAT3 Transcription Factor