Cognate Antigen-Independent Differentiation and Activation of Resident Memory T cells in Chronic Kidney Disease

• DOI: 10.1152/physiol.2024.39.s1.664
• Publication Date: 2024-05-21T14:57:50Z
• Authors: Kyle Moore; Elise Erman; Amie Traylor; Stephanie Esman; Yanlin Jiang; Jennifer LaFontaine; Anna Zmijewska
• Keywords: Cognate

Resident memory T cells (T RM s) are a subset of which retained locally within barrier and epithelial tissues such as the kidney have also been noted for their role in perpetuating chronic inflammation. While gained recognition ability to modulate inflammation various models injury s still poorly understood contributions sterile disease (CKD) unknown. We hypothesized that activated setting CKD. utilized an aristolochic acid (AA) model murine CKD investigate presence via flow cytometry characterized transcriptional profile single cell RNA sequencing (scRNAseq). measured cytokine levels with MSD plate. Six weeks after AA-induced CKD, CD8 + were significantly increased compared control mice (29.6 ± 1.6% vs. 4.7 0.6% CD45 , respectively; p<0.0001), CD4 (34.4 1.4% 8.2 0.7% CD45+, p<0.0001). 53.6 2.5% expressed CD103, marker, AA 4.8 1.2% mice, 36.0 1.7% vs 1.6 0.3% cells. Kidney protein lysates had higher IFNγ than kidneys (18.9 2.9 0.7 pg/mg, p=0.0003) well TNF (98.6 8.9 pg/mg 6.9 0.8 p=0.0002) IL-6 (247.6 39.1 75.4 22.5 p=0.0226). scRNAseq immune revealed bearing markers CD103 CD49a lacked expression tissue egress molecules S1pr1, Sell, Ccr7, Klf2. analysis this population downregulation Eomes Tbx21 transcription factors upregulation Runx3 factor, all correspond previously described profiles. next evaluated signaling pathways involved survival s, namely IL-15 TGF-β. Il2rb Il2rg (encoding receptor subunits) upregulated lysate not elevated controls (2,600 145 2,281 96 protein, p=0.0831). Tgfbr1 Tgfbr2 TGF-β TRMs, but (2,158 159 1,924 202 p=0.3886). Gene ontology pathway showed enrichment signaling. Because we assessed transgenic OT-1 can only recognize specific ovalbumin residues context MHC class 1 H-2K b . injured significant increase proportion vehicle (47.3 2.9% 9.6 p<0.0001) (26.7 3.1% 6.4 2.4% p=0.0040). Here demonstrate differentiation activation during independent cognate antigen interaction highlight profile, IFNγ, TNF, IL-6, proinflammatory cytokines typical s. Future studies will aim determine progression. F32 DK136187, T32 DK007545, R01 DK 118932, U54 DK137301. This is full abstract presented at American Physiology Summit 2024 meeting available HTML format. There no additional versions or content abstract. was peer review process.