TLR7 in B cells promotes renal inflammation and Gd-IgA1 synthesis in IgA nephropathy.

JCI Insight
Nuoyan ZhengXueqing Yu

Abstract

TLR7 has been linked to the pathogenesis of glomerulonephritis, but its precise roles are not clear. In this study, we evaluated the roles of TLR7 in IgA nephropathy (IgAN). TLR7 proteins were abundant in CD19+ B cells infiltrated in the kidneys of patients with IgAN. The intensities of both intrarenal TLR7 and CD19 proteins were closely associated with kidney function (estimated glomerular filtration rate [eGFR] and serum creatinine concentration) and renal histopathology (tubular atrophy, leukocyte infiltration, tubulointerstitial fibrosis, and global glomerulosclerosis) in patients with IgAN. Meanwhile, TLR7 mRNA levels were significantly increased in peripheral blood B cells of patients with IgAN. TLR7+CD19+ B cells expressed inflammatory cytokines (IL-6 and IL-12) in kidneys and produced high levels of IgA1 and galactose deficient-IgA1 (Gd-IgA1) in peripheral blood of patients with IgAN. Mechanistically, TLR7 activated B cells to produce high levels of Gd-IgA1 via the TLR7-GALNT2 axis in IgAN. Protein levels of GALNT2 were increased by overexpression of TLR7, while they were reduced by TLR7 knockdown in B cells. GALNT2 overexpression augmented Gd-IgA1 production in B cells derived from patients with IgAN. Taken together, h...Continue Reading

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Citations

Oct 26, 2021·Frontiers in Cellular and Infection Microbiology·Yuanfa FengJun Huang
Nov 14, 2021·Clinical and Experimental Nephrology·Keiichi MatsuzakiYusuke Suzuki

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Methods Mentioned

BETA
biopsy
biopsies
PCR
ELISA
transfection

Software Mentioned

GraphPad Prism
Zeiss
Excel
Primer
SPSS
SDS2

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