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Effect of CD40/CD40L signaling on IL-10-producing regulatory B cells in Chinese children with Henoch-Schönlein purpura nephritis

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Abstract

The aim of the present study was to examine the role and mechanism of interleukin-10 (IL-10)-producing regulatory B cells (B10 cells) in the pathogenesis of Henoch-Schönlein purpura nephritis (HSPN). We examined the percentage of B10 cells, CD19+CD24hiCD38hi B cells, CD19+CD24hiCD27+ B cells, Th17 cells, and T regulatory (Treg) cells within the peripheral blood mononuclear cell (PBMC) population in healthy subjects and HSP/HSPN patients. The percentage of B10 cells and CD19+CD24hiCD38hi B cells was reduced in HSPN patients and that of CD19+CD24hiCD27+ B cells was decreased only in HSPN patients with hematuria and proteinuria or massive proteinuria. The expression of IL-10 by B10 cells and their subsets was decreased in HSPN patients and returned to normal levels in HSP/HSPN patients in remission. B10 cells and their subsets negatively correlated with the Th17/Treg ratio. There was no difference in B10pro + B10 cells, Th17 cells, Treg cells, and the Th17/Treg ratio between children with HSP/HSPN and healthy controls after CD40L stimulation. On the other hand, the level of IL-10 expressed by CD19+CD40+ B cells was decreased in HSPN, and the percentage of B10pro + B10 cells and Treg cells was reduced and that of Th17 cell was increased in the presence of anti-CD40L monoclonal antibody (mAb). Thus, decreased B10 cells and CD19+CD24hiCD38hi B cells may function as an early marker of renal impairment in HSPN. The dysfunction of B10 cells may play a role in the pathogenesis of HSPN by regulating the Th17/Treg balance. Moreover, the CD40/CD40L signaling pathway may play a role in B10 cell differentiation and functional maturation.

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Acknowledgment

This work was supported by the National Natural Science Foundation of China (Grant No. 81470946). We thank the patients, donors, and their families for their cooperation. We also thank Professors Guo-Bing Wang and Hong-Qiang Du for help with flow cytometry.

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Authors and Affiliations

  1. Ministry of Education, Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, China

    Baohui Yang, Xiongjun Tan, Xiao Xiong, Shifang Dong & Wei Liu

  2. Department of Nephroimmunology, Children’s Hospital, Chongqing Medical University, Chongqing, China

    Daoqi Wu, Gaofu Zhang, Mo Wang, Haiping Yang & Qiu Li

  3. The Central Laboratory of Children’s Hospital, Chongqing Medical University, Chongqing, China

    Shifang Dong

  4. Children’s Hospital of Chongqing Medical University, 136 Second Zhongshan Road, Yuzhong District, Chongqing, 400014, People’s Republic of China

    Haiping Yang & Qiu Li

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  1. Baohui Yang
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All procedures performed in studies involving human materials were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

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Yang, B., Tan, X., Xiong, X. et al. Effect of CD40/CD40L signaling on IL-10-producing regulatory B cells in Chinese children with Henoch-Schönlein purpura nephritis. Immunol Res 65, 592–604 (2017). https://doi.org/10.1007/s12026-016-8877-8

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