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Current Molecular Medicine

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ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

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Research Article

Follicular Helper T Cells in Peyer's Patches and Galactose- Deficient Iga1 Contribute to Iga Nephropathy

Author(s): Yuye Huang, Xunling Sun, Guoming Nie, Hongtao Xu and Minshu Zou*

Volume 24, Issue 8, 2024

Published on: 12 September, 2023

Page: [1033 - 1044] Pages: 12

DOI: 10.2174/1566524023666230720112215

Price: $65

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Abstract

Background: Common primary glomerulonephritis with aberrant mucosal immunity is IgA nephropathy (IgAN). T follicular helper (TFH) cells are essential in regulating B cell differentiation. Peyer’s patches (PPs) are the main site where IgA+ plasmablasts differentiate.

Objective: Our study aimed to investigate the TFH cell's potential contribution to the etiology of IgA nephropathy.

Methods: In PPs from IgAN mouse models, the ratio of the TFH cell, B220+IgA+, B220+IgM+, and B220-IgA+ lymphocytes were assessed. Then, we used Western blot to assess the expression of Bcl-6, Blimp- 1, and IL-21 proteins in PPs and used RTPCR to assess the expression of IL-21 and TGF-β1 mRNA. TFH cells coculture with spleen cells to measure the degree of IL-21 and the ratio of activation marker CD69 on the TFH cells. Naive B cells (CD27-IgD+) from children suffering from IgAN were cultured with TFH cell-related cytokines. The supernatant was detected to assess the excretion of galactose-deficient IgA1 (Gd-IgA1).

Results: IgAN mice developed noticeably increased degrees of IL-21 and CD69 on TFH cells than controls did, as well as higher percentages of B220+IgA+, B220+IgM+, B220+IgA+, TGF- β1, and IL-21 mRNA and Bcl-6, IL-21 proteins in PPs. The Gd-IgA1 level in the supernatant and IgAN- positive children's serum were noticeably higher than those of the healthy controls (P < 0.05). PPs provide the microenvironment to induce the production of IgA-secreting plasmablasts.

Conclusion: TFH cells may be a key moderator to induce B cell differentiation into IgAsecreting plasmablasts and produce Gd-IgA1, which plays a significant part in IgAN’s pathogenesis. It could be a new therapeutic target in the future.

Keywords: IgA nephropathy, Peyer’s patches, T follicular helper cell, CD4 T Cells, Interleukin-21, Galactosedeficient IgA1.

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