# RNA binding proteins in end-organ autoimmune pathology

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2022 · $633,244

## Abstract

IL-17 and Th17 cells are dysregulated in many pathologic auto-inflammatory conditions.
Antibody-mediated glomerulonephritis (AGN) occurs when unchecked inflammation triggered by
autoimmune Ab complexes that deposit in glomeruli and lead to kidney damage, which occurs in
conditions such as Goodpasture disease, ANCA vasculitis, etc. Although the initiators of
autoantibody-mediated pathology differ, the terminal events in end organ kidney damage have
many common hallmarks, and the fundamental immunology of this process is still not well
understood. Accumulating evidence from our groups and others have convincingly demonstrated
role for IL-17 in driving pathogenesis of AGN in humans and in mouse models. Excessive
autoimmune pathology can be caused by hyper-production of cytokines from T helper cells or by
over-exuberant cytokine signaling. Therefore, in principle, molecules that influence IL-17 signal
transduction have the potential to be viable targets for therapy in settings where this cytokine is a
disease driver. In probing the fundamental mechanisms that mediate IL-17-dependent signaling,
we identified two novel RNA binding proteins (RBPs) that contribute significantly to the
pathogenesis of AGN in vivo. These RBPs are downstream of IL-17 and their activities in the IL-
17 pathway are interconnected through regulation of CCAAT Enhancer Binding Protein (C/EBP)
transcription factors. In turn, C/EBPs mediate IL-17-dependent effectors that promote renal
inflammation, including Lipocalin-2, neutrophil-recruiting chemokines, and feed-forward activators
of Th17 differentiation such as IL-6. Our central hypothesis is that IL-17 promotes inflammation
through post-transcriptional regulation of downstream mRNAs that drive renal pathology in AGN.
This proposal will evaluate the molecular mechanisms by which these RBPs act and the specific
physiological functions in the setting of AGN.

## Key facts

- **NIH application ID:** 10450945
- **Project number:** 1R01AI162616-01A1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Partha Sarathi Biswas
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $633,244
- **Award type:** 1
- **Project period:** 2022-02-08 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10450945

## Citation

> US National Institutes of Health, RePORTER application 10450945, RNA binding proteins in end-organ autoimmune pathology (1R01AI162616-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10450945. Licensed CC0.

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