Endogenous IL-22 is dispensable for experimental glomerulonephritis
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Endogenous IL-22 is dispensable for experimental glomerulonephritis. / Gnirck, Ann-Christin; Wunderlich, Malte; Becker, Martina; Xiong, Tingting; Weinert, Ella; Meyer-Schwesinger, Catherine; Dumoutier, Laure; Renauld, Jean-Christophe; Huber, Samuel; Panzer, Ulf; Turner, Jan-Eric.
In: AM J PHYSIOL-RENAL, Vol. 316, No. 4, 01.04.2019, p. F712-F722.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Endogenous IL-22 is dispensable for experimental glomerulonephritis
AU - Gnirck, Ann-Christin
AU - Wunderlich, Malte
AU - Becker, Martina
AU - Xiong, Tingting
AU - Weinert, Ella
AU - Meyer-Schwesinger, Catherine
AU - Dumoutier, Laure
AU - Renauld, Jean-Christophe
AU - Huber, Samuel
AU - Panzer, Ulf
AU - Turner, Jan-Eric
PY - 2019/4/1
Y1 - 2019/4/1
N2 - In recent years, the cytokine interleukin (IL)-22 attracted considerable attention due to its important immunoregulatory function in barrier tissues, such as the gut, lung, and skin. Although a regenerative role of IL-22 in renal tubular damage has been demonstrated, the role of IL-22 in the immunopathogenesis of glomerular injury is still unknown. Here, we demonstrate that the IL-22 receptor is expressed in the glomerular compartment of the kidney and that IL-22 expression increases in the renal cortex after induction of glomerular injury in a mouse model for crescentic glomerulonephritis (cGN, nephrotoxic nephritis). We identified γδ T cells and T H17 cells as major sources for IL-22 in the nephritic kidney. However, neither genetic or antibody-mediated deletion of IL-22 nor genetic deficiency in its endogenous inhibitor IL-22Rα2 (IL-22 binding protein) resulted in substantial phenotypic differences in mice with cGN with respect to crescent formation, tubulointerstitial damage, and kidney function impairment. Similarly, we did not observe significant differences between wild-type or IL-22-deficient mice in a mouse model of secondary focal and segmental glomerulosclerosis (adriamycin-induced nephropathy). As shown previously, we detected concomitant upregulation of IL-17A and IFN-γ production by T cells during the course of cGN, providing alternative cytokine pathways that mediate glomerular injury in this model. In conclusion, we show here that endogenous IL-22 expression is redundant in different forms of glomerular injury, indicating that the IL-22-directed therapies that are being tested in various human diseases might not affect the kidney in patients with glomerular disease.
AB - In recent years, the cytokine interleukin (IL)-22 attracted considerable attention due to its important immunoregulatory function in barrier tissues, such as the gut, lung, and skin. Although a regenerative role of IL-22 in renal tubular damage has been demonstrated, the role of IL-22 in the immunopathogenesis of glomerular injury is still unknown. Here, we demonstrate that the IL-22 receptor is expressed in the glomerular compartment of the kidney and that IL-22 expression increases in the renal cortex after induction of glomerular injury in a mouse model for crescentic glomerulonephritis (cGN, nephrotoxic nephritis). We identified γδ T cells and T H17 cells as major sources for IL-22 in the nephritic kidney. However, neither genetic or antibody-mediated deletion of IL-22 nor genetic deficiency in its endogenous inhibitor IL-22Rα2 (IL-22 binding protein) resulted in substantial phenotypic differences in mice with cGN with respect to crescent formation, tubulointerstitial damage, and kidney function impairment. Similarly, we did not observe significant differences between wild-type or IL-22-deficient mice in a mouse model of secondary focal and segmental glomerulosclerosis (adriamycin-induced nephropathy). As shown previously, we detected concomitant upregulation of IL-17A and IFN-γ production by T cells during the course of cGN, providing alternative cytokine pathways that mediate glomerular injury in this model. In conclusion, we show here that endogenous IL-22 expression is redundant in different forms of glomerular injury, indicating that the IL-22-directed therapies that are being tested in various human diseases might not affect the kidney in patients with glomerular disease.
KW - Journal Article
U2 - 10.1152/ajprenal.00303.2018
DO - 10.1152/ajprenal.00303.2018
M3 - SCORING: Journal article
C2 - 30724106
VL - 316
SP - F712-F722
JO - AM J PHYSIOL-RENAL
JF - AM J PHYSIOL-RENAL
SN - 1931-857X
IS - 4
ER -