Work

Immune-mediated mechanisms of kidney injury and fibrosis in the absence of a functional cystic fibrosis transmembrane conductance regulator (CFTR) 2979

Year: 2025

Type: article

Abstract: Description Despite its high expression in renal tubular cells, the role of CFTR in renal repair and injury is unknown. We showed that adults with cystic fibrosis (CF), a disease caused by dysfunctional CFTR, have increased urinary levels of tubular injury markers. However, the nature of the tubular injury and its effects on renal immune responses in CF are unknown. ScRNA-seq of kidneys from 2-month-old mice that harbor the most common CFTR mutation F508del and wild-type mice revealed an injured proximal tubule segment 3 cluster in F508del kidneys. Both proximal and distal tubules had increased expression of TGFβ profibrotic pathways in F508del kidneys. The most highly expressed gene was Txnip, whose increased expression was confirmed by immunoblot. In support of fibrotic processes, there was an expansion of Spp1 (osteopontin) and fibronectin (Fn1) expressing macrophages. Flow cytometry showed fewer and less proliferative F4/80+MHCII+CD163+ macrophages. Among lymphocytes, CD4 and CD8 T cells were significantly higher in F508del kidneys. CD4+ Th1 (Cxcr3), cytotoxic CD8 + (Gzmb), and exhausted CD8 + (Pd-1) T cells were also increased, phenotypes previously linked to kidney fibrosis. Notably, γδT cells harbored a tissue-resident memory phenotype and were increased in F508del kidneys. These findings reveal that CFTR dysfunction promotes tubular injury, profibrotic signaling, and a pro-inflammatory immune environment, highlighting its role in renal immune regulation and repair processes. Funding Sources Cystic Fibrosis Foundation MPI Research Award “Kidney Function in PwCF in the Era of HEMT” (SKOPEL24A0-MPI) Topic Categories Cellular Adhesion, Migration, and Inflammation (CAM)

Source: The Journal of Immunology

DOI: 10.1093/jimmun/vkaf283.830

Authors: Himanshu Ballav Goswami, Tom Harris, Agnieszka Swiatecka-Urban, Sladjana Skopelja-Gardner

Institutions: Dartmouth College, University of Alabama at Birmingham, University of Virginia

Language: English

Topic: Cystic Fibrosis Research Advances

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: bronze

OpenAlex ID: W4416447978