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Intrinsic renal cells induce lymphocytosis of Th22 cells from IgA nephropathy patients through B7–CTLA-4 and CCL-CCR pathways

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Abstract

IgA nephropathy (IgAN), the most common glomerulonephritis, has an unclear pathogenesis. The role of Th22 cells, which are intimately related to proteinuria and progression in IgAN, in mediating infection-related IgAN is unclear. This study aimed to characterize the association between intrinsic renal cells (tubular epithelial cells and mesangial cells) and Th22 cells in immune regulation of infection-related IgAN and to elucidate the impact of Th22 lymphocytosis; the proinflammatory cytokines IL-1, IL-6, and TNF-α; and CCL chemokines on kidney fibrosis. Hemolytic streptococcus infection induced an increase in IL-1, IL-6, and TNF-α, resulting in Th22 cell differentiation from T lymphocytes obtained from patients with IgAN, and the CCL20–CCR6, CCL22–CCR4, and/or CCL27–CCR10 axes facilitated Th22 cell chemotaxis. The increased amount of Th22 cells caused an increase in TGF-β1 levels, and anti-CD80, anti-CD86, and CTLA-4Ig treatment reduced TGF-β1 levels by inhibiting Th22 lymphocytosis and secretion of cytokines and chemokines, thus potentially relieving kidney fibrosis. Our data suggest that Th22 cells might be recruited into the kidneys via the CCL20–CCR6, CCL22–CCR4, and/or CCL27–CCR10 axes by mesangial cells and tubular epithelial cells in infection-related IgAN. Th22 cell overrepresentation was attributed to stimulation of the B7–CTLA-4Ig antigen-presenting pathway and IL-1, IL-6, and TNF-α.

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Acknowledgements

This work was supported by Grants from the National Natural Science Foundation of China (Nos. 81470933 and 81270786) (http://www.nsfc.gov.cn/).

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Author notes

  1. Qiaoling Zhou, Xiaozhao Li, Ting Meng, Jiaxi Pu, Mengyuan Zhu, and Chenggen Xiao have contributed equally to this work.

Authors and Affiliations

  1. Department of Nephrology, Xiangya Hospital, Central South University, Changsha, Hunan, China

    Lu Gan, Qiaoling Zhou, Xiaozhao Li, Chen Chen, Ting Meng, Jiaxi Pu, Mengyuan Zhu & Chenggen Xiao

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  1. Lu Gan
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  2. Qiaoling Zhou
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  3. Xiaozhao Li
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Correspondence to Lu Gan.

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This study protocol was approved by the Medical Ethics Committee of the Xiangya Hospital of Central South University for Human Studies (Approval Number 201403270).

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Gan, L., Zhou, Q., Li, X. et al. Intrinsic renal cells induce lymphocytosis of Th22 cells from IgA nephropathy patients through B7–CTLA-4 and CCL-CCR pathways. Mol Cell Biochem 441, 191–199 (2018). https://doi.org/10.1007/s11010-017-3185-8

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  • DOI: https://doi.org/10.1007/s11010-017-3185-8

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