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SIT1 identifies circulating hypoactive T cells with elevated cytotoxic molecule secretion in systemic lupus erythematosus patients

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Abstract

This study aims to elucidate the expression and functionality of SIT1 in circulating CD8/CD4 + T cells in humans and to delineate its significance in systemic lupus erythematosus (SLE) patients. We employed multiparametric flow cytometry to investigate the expression of SIT1 in circulating CD8/CD4 + T cells and their respective subsets, comparing healthy controls (HCs) with SLE patients. Furthermore, we assessed the levels of granzyme B, perforin, IL-17, and IFN-γ in SIT1-related CD8/CD4 + T cells from both HCs and SLE patients, both before and after PMA stimulation. Clinically, we conducted receiver operating characteristic curve analysis and correlation analysis to evaluate the clinical relevance of SIT1-related CD8/CD4 + T cells in SLE patients. SIT1 exhibited higher expression in CD4 + T cells, with SIT1 − T cells demonstrating elevated levels of granzyme B, perforin, and IFN-γ compared to SIT1 + T cells. PMA-stimulated T cells exhibited reduced SIT1 expression compared to unstimulated T cells. SLE patients displayed increased SIT1 + proportions in CD8 + T cells and decreased SIT1 + CD4 + T cell numbers. Additionally, SIT1 + cells in SLE patients exhibited significantly higher levels of granzyme B and perforin compared to HCs. SIT1 + cells demonstrated significant associations with clinical indicators in SLE patients, with indicators related to SIT1 proving valuable in the diagnosis of SLE patients. SIT1 is inversely correlated with T cell activation. In SLE patients, SIT1 expression is altered in T cells concomitant with an augmented secretion of cytotoxic molecules. This upregulation may contribute to the pathogenesis of SLE and enhance its diagnostic potential.

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Data availability

The data of this study are available from the corresponding author upon reasonable request.

Abbreviations

SIT1 :

Signaling threshold regulating transmembrane adaptor 1

SLE :

Systemic lupus erythematosus

HC :

Healthy control

TEM :

Effector memory T cell

TEMRA :

Effector memory T cells reexpressing CD45RA

TCM :

Central memory cell

Tn :

Naive T cell

MFI :

Mean fluorescence intensity

NF-AT :

Nuclear factor of T cells

PBMC :

Peripheral blood mononuclear cells

PKC :

Protein kinase C

PLC :

Phospholipase C

C4 :

Complement component 4

CRP :

C-Reactive Protein

ESR :

Erythrocyte sedimentation rate

FBS :

Fetal bovine serum

GZMB :

Granzyme B

IgA :

Immunoglobulin A

IgG :

Immunoglobulin G

IgM :

Immunoglobulin M

ITIMs :

Immunoreceptor tyrosine-based inhibitory motifs

AUC :

Area under the curve

ROC :

Receiver operating characteristic curve

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Funding

This work was supported by grants from the National Natural Science Foundation of China (82271755, 81871230) and Peking University People’s Hospital Scientific Research Development Funds (RZ 2022–06).

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Author notes

  1. Ainizati Hasimu and Ayibaota Bahabayi contributed equally to the work.

Authors and Affiliations

  1. Department of Clinical Laboratory, Peking University People’s Hospital, 11# Xizhimen South Street, Beijing, China

    Ainizati Hasimu, Ayibaota Bahabayi, Ziqi Xiong, Qi Li, Zhonghui Zhang, Xingyue Zeng & Chen Liu

  2. School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China

    Mohan Zheng & Zihang Yuan

Authors
  1. Ainizati Hasimu
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  2. Ayibaota Bahabayi
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  4. Qi Li
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  5. Zhonghui Zhang
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  6. Xingyue Zeng
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  7. Mohan Zheng
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  8. Zihang Yuan
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  9. Chen Liu
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Contributions

CL took charge of all the work and participated in its design. AB and AH conducted most of the experiments and drafted the manuscript. QL and ZZ analyzed the data. XZ and MZ did part of the cellular experiments. ZY did part of the clinical measurements. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Chen Liu.

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Hasimu, A., Bahabayi, A., Xiong, Z. et al. SIT1 identifies circulating hypoactive T cells with elevated cytotoxic molecule secretion in systemic lupus erythematosus patients. Immunol Res (2024). https://doi.org/10.1007/s12026-024-09481-w

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