Targeting monocyte derived CCL17 attenuates murine crescentic glomerulonephritis by affecting renal CCR4+ regulatory T cell recruitment
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Targeting monocyte derived CCL17 attenuates murine crescentic glomerulonephritis by affecting renal CCR4+ regulatory T cell recruitment. / Song, Ning; Paust, Hans-Joachim; Asada, Nariaki; Peters, Anett; Kaffke, Anna; Krebs, Christian F; Panzer, Ulf; Riedel, Jan-Hendrik.
In: AM J NEPHROL, Vol. 55, No. 2, 2024, p. 214-224.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Targeting monocyte derived CCL17 attenuates murine crescentic glomerulonephritis by affecting renal CCR4+ regulatory T cell recruitment
AU - Song, Ning
AU - Paust, Hans-Joachim
AU - Asada, Nariaki
AU - Peters, Anett
AU - Kaffke, Anna
AU - Krebs, Christian F
AU - Panzer, Ulf
AU - Riedel, Jan-Hendrik
N1 - S. Karger AG, Basel.
PY - 2024
Y1 - 2024
N2 - INTRODUCTION: The chemokine receptor CCR4 is expressed by diverse CD4+ T cell subsets including regulatory T cells (Tregs) but its functional importance for leukocyte recruitment and the relevance of its two corresponding chemokines CCL17 and CCL22 have not been studied in immune-mediated crescentic glomerulonephritis (cGN).METHODS: Utilizing the single-cell RNA sequencing (scRNAseq) data in analyzing leukocytes isolated from both human and murine nephritic kidneys, we identified CCL17 as a potential therapeutic target in immune-mediated renal disease. Using a mouse model of murine cGN, we then delineated the effects of targeting CCL17 by neutralizing antibodies and in Ccl17 gene-deficient mice.RESULTS: Unsupervised scRNAseq analyses identified the CCL17-CCR4 axis as a mechanism potentially involved in renal T-cell migration. Analyses of functional kidney impairment and histopathological kidney damage revealed an attenuation of crescentic GN in anti-CCL17 antibody-treated mice which was corroborated using in Ccl17 gene-deficient mice. Immunohistochemical analyses revealed that these changes were accompanied by an affected renal Treg recruitment in both experimental approaches.CONCLUSION: The chemokine receptor CCR4 and its corresponding chemokine CCL17 are expressed in human and murine cGN and targeting the CCR4-CCL17 axis by neutralizing antibodies as well as Ccl17 gene deficiency led to increased renal Treg recruitment and reduced histological and functional kidney damage in murine cGN.
AB - INTRODUCTION: The chemokine receptor CCR4 is expressed by diverse CD4+ T cell subsets including regulatory T cells (Tregs) but its functional importance for leukocyte recruitment and the relevance of its two corresponding chemokines CCL17 and CCL22 have not been studied in immune-mediated crescentic glomerulonephritis (cGN).METHODS: Utilizing the single-cell RNA sequencing (scRNAseq) data in analyzing leukocytes isolated from both human and murine nephritic kidneys, we identified CCL17 as a potential therapeutic target in immune-mediated renal disease. Using a mouse model of murine cGN, we then delineated the effects of targeting CCL17 by neutralizing antibodies and in Ccl17 gene-deficient mice.RESULTS: Unsupervised scRNAseq analyses identified the CCL17-CCR4 axis as a mechanism potentially involved in renal T-cell migration. Analyses of functional kidney impairment and histopathological kidney damage revealed an attenuation of crescentic GN in anti-CCL17 antibody-treated mice which was corroborated using in Ccl17 gene-deficient mice. Immunohistochemical analyses revealed that these changes were accompanied by an affected renal Treg recruitment in both experimental approaches.CONCLUSION: The chemokine receptor CCR4 and its corresponding chemokine CCL17 are expressed in human and murine cGN and targeting the CCR4-CCL17 axis by neutralizing antibodies as well as Ccl17 gene deficiency led to increased renal Treg recruitment and reduced histological and functional kidney damage in murine cGN.
U2 - 10.1159/000534151
DO - 10.1159/000534151
M3 - SCORING: Journal article
C2 - 37742620
VL - 55
SP - 214
EP - 224
JO - AM J NEPHROL
JF - AM J NEPHROL
SN - 0250-8095
IS - 2
ER -