Follicular Helper T Cells In Peyer's Patches And Galactose-Deficient Iga1 Contribute To Iga Nephropathy.
Curr Mol Med
; 2023 Jul 20.
Article
em En
| MEDLINE
| ID: mdl-37475555
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. MATERIALS ANDMETHODS:
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 RT-PCR to assess the expression of IL-21 and TGF- 1 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- 1, 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 IgA-secreting plasmablasts and produce Gd-IgA1, which plays a significant part in IgAN's pathogenesis. It could be a new therapeutic target in the future.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Curr Mol Med
Ano de publicação:
2023
Tipo de documento:
Article