Instruct: Identify the main category of Biorxiv papers based on the titles and abstracts
Query: Antibody-induced glomerulonephritis is amplified by RTEC-intrinsic IL-17 signaling and restrained by IL-17-mediated induction of the endoribonuclease Regnase-1 (Zc3h12a) Antibody-mediated glomerulonephritis (AGN) is a clinical manifestation of many autoimmune kidney diseases for which few effective treatments exist. Chronic inflammatory circuits in renal glomerular and tubular cells lead to tissue damage in AGN. These cells are targeted by the cytokine IL-17, which has recently been shown to be a central driver of the pathogenesis of AGN. However, surprisingly little is known about the regulation of pathogenic IL-17 signaling in the kidney. Here, using a well characterized mouse model of AGN, we show that IL-17 signaling in renal tubular epithelial cells (RTECs) is necessary for AGN development. We also show that Regnase-1, an RNA binding protein with endoribonuclease activity, is a negative regulator of IL-17 signaling in RTECs. Accordingly, mice with a selective Regnase-1 deficiency in RTECs exhibited exacerbated kidney dysfunction in AGN. Mechanistically, Regnase-1 inhibits IL-17-driven expression of the transcription factor I{kappa}B{xi} and consequently its downstream gene targets including Il6 and Lcn2. Moreover, deletion of Regnase-1 in human RTECs reduced inflammatory gene expression in an I{kappa}B{xi}-dependent manner. Overall, these data identify an IL-17-driven inflammatory circuit in RTECs during AGN that is constrained by Regnase-1.
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The categories of this paper are: molecular
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The categories of this paper are: bioengineering
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The categories of this paper are: synthetic
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The categories of this paper are: neuroscience
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The categories of this paper are: evolutionary
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The categories of this paper are: animal
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The categories of this paper are: behavior
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The categories of this paper are: pathology
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The categories of this paper are: bioinformatics
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The categories of this paper are: biophysics
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The categories of this paper are: microbiology
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The categories of this paper are: scientific
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The categories of this paper are: biochemistry
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The categories of this paper are: ecology
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The categories of this paper are: epidemiology
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The categories of this paper are: physiology