Proinflammatory plasticity towards Th17 paradigm of regulatory T cells consistent with elevated prevalence of TGFBR2 variants in elderly patients with primary immune thrombocytopenia

BMC Immunology - Tập 24 Số 1
Jingjing Cao1, Yanxia Zhan1, Lili Ji1, Pu Chen2, Luya Cheng1, Feng Li1, Xibing Zhuang3, Zhihui Min4, Lihua Sun5, Fanli Hua5, Hao Chen6, Boting Wu7, Yunfeng Cheng3
1Department of Hematology, Zhongshan Hospital Fudan University, Shanghai, 200032, China
2Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
3Center for Tumor Diagnosis and Therapy, Jinshan Hospital, Fudan University, Shanghai, 201508, China
4Institute of Clinical Science, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
5Department of Hematology, Zhongshan Hospital Qingpu Branch, Fudan University, Shanghai, 201700, China
6Department of Thoracic Surgery, Zhongshan Hospital Xuhui Branch, Fudan University, Shanghai, 200031, China
7Department of Transfusion, Zhongshan Hospital, Fudan University, Shanghai, 200032, China

Tóm tắt

Abstract Background Primary immune thrombocytopenia (ITP) is characterized for the skewed Th differentiation towards Th1 and Th17 cells as well as the impaired number and function of regulatory T cells (Tregs). Tregs are capable of co-expressing effector Th markers in different inflammatory milieu, which probably indicates Treg dysfunction and incompetence to counter over-activated immune responses. Methods Ninety-two primary ITP patients from March 2013 to December 2018 were included, and proinflammatory plasticity in different Treg compartments, age groups, and TGFBR2 variant carrier status were investigated. Results Patients were categorized into elderly (n = 44) and younger (n = 48) groups according to an age of 50 years at disease onset. The overall remission rate was 82.6% after first-line regimens, including 47.8% complete remission. TGFBR2 variants were found in 7 (7.6%) patients with three V216I and four T340M heterozygote carriers. ITP patients demonstrated elevated co-expression of IL-17 and decreased co-expression of both IFN-γ and IL-13 than health control (all p < 0.01). The elderly group demonstrated elevated prevalence of TGFBR2 variants (p = 0.037) and elevated co-expression of IL-17 (p = 0.017) in Tregs, while female predominance was found in the younger group (p = 0.037). In the elderly group, TGFBR2 variant carriers demonstrated further elevated co-expression of IL-17 (p = 0.023) and decreased co-expression of both IFN-γ (p = 0.039) and IL-13 (p = 0.046) in the aTreg compartment. Conclusions Our findings revealed additional aberrations of Treg proinflammatory plasticity in elderly primary ITP patients, and highlighted the potential role of Treg dysfunction and senescence in the pathogenesis and management among these patients.

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BMC Immunology

Tập 24 Số 1

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