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The CCR6/CCL20 Axis Expands RORγt+ Tregs to Protect from Glomerulonephritis

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The CCR6/CCL20 Axis Expands RORγt+ Tregs to Protect from Glomerulonephritis. / Herrnstadt, Georg R; Niehus, Christoph B; Ramcke, Torben; Hagenstein, Julia; Ehnold, Laura-Isabell; Nosko, Anna; Warkotsch, Matthias T; Feindt, Frederic C; Melderis, Simon; Paust, Hans-Joachim; Sivayoganathan, Varshi; Jauch-Speer, Saskia-Larissa; Wong, Milagros N; Indenbirken, Daniela; Krebs, Christian F; Huber, Tobias B; Panzer, Ulf; Puelles, Victor G; Kluger, Malte A; Steinmetz, Oliver M.

In: KIDNEY INT, Vol. 104, No. 1, 07.2023, p. 74-89.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Herrnstadt, GR, Niehus, CB, Ramcke, T, Hagenstein, J, Ehnold, L-I, Nosko, A, Warkotsch, MT, Feindt, FC, Melderis, S, Paust, H-J, Sivayoganathan, V, Jauch-Speer, S-L, Wong, MN, Indenbirken, D, Krebs, CF, Huber, TB, Panzer, U, Puelles, VG, Kluger, MA & Steinmetz, OM 2023, 'The CCR6/CCL20 Axis Expands RORγt+ Tregs to Protect from Glomerulonephritis', KIDNEY INT, vol. 104, no. 1, pp. 74-89. https://doi.org/10.1016/j.kint.2023.02.027

APA

Herrnstadt, G. R., Niehus, C. B., Ramcke, T., Hagenstein, J., Ehnold, L-I., Nosko, A., Warkotsch, M. T., Feindt, F. C., Melderis, S., Paust, H-J., Sivayoganathan, V., Jauch-Speer, S-L., Wong, M. N., Indenbirken, D., Krebs, C. F., Huber, T. B., Panzer, U., Puelles, V. G., Kluger, M. A., & Steinmetz, O. M. (2023). The CCR6/CCL20 Axis Expands RORγt+ Tregs to Protect from Glomerulonephritis. KIDNEY INT, 104(1), 74-89. https://doi.org/10.1016/j.kint.2023.02.027

Vancouver

Herrnstadt GR, Niehus CB, Ramcke T, Hagenstein J, Ehnold L-I, Nosko A et al. The CCR6/CCL20 Axis Expands RORγt+ Tregs to Protect from Glomerulonephritis. KIDNEY INT. 2023 Jul;104(1):74-89. https://doi.org/10.1016/j.kint.2023.02.027

Bibtex

@article{1dbfa5c5613043ed9f42d988007060d0,
title = "The CCR6/CCL20 Axis Expands RORγt+ Tregs to Protect from Glomerulonephritis",
abstract = "Previous studies have identified a unique Treg population, which expresses the Th17 characteristic transcription factor RORγt. These RORγt+ Tregs possess enhanced immunosuppressive capacity, which endows them with great therapeutic potential. However, as a caveat, they are also capable of secreting pro-inflammatory IL-17A. Since the sum function of RORγt+ Tregs in glomerulonephritis (GN) remains unknown, we studied the effects of their absence. Purified CD4+ T cell populations, containing or lacking RORγt+ Tregs, were transferred into immunocompromised RAG1 knockout mice and the nephrotoxic nephritis model of GN was induced. Absence of RORγt+ Tregs significantly aggravated kidney injury, demonstrating overall kidney-protective properties. Analyses of immune responses showed, that RORγt+ Tregs were broadly immunosuppressive with no preference for a particular type of T cell response. Further characterization revealed a distinct functional and transcriptional profile, including enhanced production of IL-10. Expression of the chemokine receptor CCR6 marked a particularly potent subset, whose absence significantly worsened GN. As an underlying mechanism, we found that chemokine CCL20 acting through receptor CCR6 signaling mediated expansion and activation of RORγt+ Tregs. Finally, we also detected an increase of CCR6+ Tregs in kidney biopsies, as well as enhanced secretion of chemokine CCL20 in 21 patients with anti-neutrophil cytoplasmic antibody associated GN compared to that of 31 healthy living donors, indicating clinical relevance. Thus, our data characterize RORγt+ Tregs as anti-inflammatory mediators of GN and identify them as promising target for Treg directed therapies.",
author = "Herrnstadt, {Georg R} and Niehus, {Christoph B} and Torben Ramcke and Julia Hagenstein and Laura-Isabell Ehnold and Anna Nosko and Warkotsch, {Matthias T} and Feindt, {Frederic C} and Simon Melderis and Hans-Joachim Paust and Varshi Sivayoganathan and Saskia-Larissa Jauch-Speer and Wong, {Milagros N} and Daniela Indenbirken and Krebs, {Christian F} and Huber, {Tobias B} and Ulf Panzer and Puelles, {Victor G} and Kluger, {Malte A} and Steinmetz, {Oliver M}",
note = "Copyright {\textcopyright} 2023. Published by Elsevier Inc.",
year = "2023",
month = jul,
doi = "10.1016/j.kint.2023.02.027",
language = "English",
volume = "104",
pages = "74--89",
journal = "KIDNEY INT",
issn = "0085-2538",
publisher = "NATURE PUBLISHING GROUP",
number = "1",

}

RIS

TY - JOUR

T1 - The CCR6/CCL20 Axis Expands RORγt+ Tregs to Protect from Glomerulonephritis

AU - Herrnstadt, Georg R

AU - Niehus, Christoph B

AU - Ramcke, Torben

AU - Hagenstein, Julia

AU - Ehnold, Laura-Isabell

AU - Nosko, Anna

AU - Warkotsch, Matthias T

AU - Feindt, Frederic C

AU - Melderis, Simon

AU - Paust, Hans-Joachim

AU - Sivayoganathan, Varshi

AU - Jauch-Speer, Saskia-Larissa

AU - Wong, Milagros N

AU - Indenbirken, Daniela

AU - Krebs, Christian F

AU - Huber, Tobias B

AU - Panzer, Ulf

AU - Puelles, Victor G

AU - Kluger, Malte A

AU - Steinmetz, Oliver M

N1 - Copyright © 2023. Published by Elsevier Inc.

PY - 2023/7

Y1 - 2023/7

N2 - Previous studies have identified a unique Treg population, which expresses the Th17 characteristic transcription factor RORγt. These RORγt+ Tregs possess enhanced immunosuppressive capacity, which endows them with great therapeutic potential. However, as a caveat, they are also capable of secreting pro-inflammatory IL-17A. Since the sum function of RORγt+ Tregs in glomerulonephritis (GN) remains unknown, we studied the effects of their absence. Purified CD4+ T cell populations, containing or lacking RORγt+ Tregs, were transferred into immunocompromised RAG1 knockout mice and the nephrotoxic nephritis model of GN was induced. Absence of RORγt+ Tregs significantly aggravated kidney injury, demonstrating overall kidney-protective properties. Analyses of immune responses showed, that RORγt+ Tregs were broadly immunosuppressive with no preference for a particular type of T cell response. Further characterization revealed a distinct functional and transcriptional profile, including enhanced production of IL-10. Expression of the chemokine receptor CCR6 marked a particularly potent subset, whose absence significantly worsened GN. As an underlying mechanism, we found that chemokine CCL20 acting through receptor CCR6 signaling mediated expansion and activation of RORγt+ Tregs. Finally, we also detected an increase of CCR6+ Tregs in kidney biopsies, as well as enhanced secretion of chemokine CCL20 in 21 patients with anti-neutrophil cytoplasmic antibody associated GN compared to that of 31 healthy living donors, indicating clinical relevance. Thus, our data characterize RORγt+ Tregs as anti-inflammatory mediators of GN and identify them as promising target for Treg directed therapies.

AB - Previous studies have identified a unique Treg population, which expresses the Th17 characteristic transcription factor RORγt. These RORγt+ Tregs possess enhanced immunosuppressive capacity, which endows them with great therapeutic potential. However, as a caveat, they are also capable of secreting pro-inflammatory IL-17A. Since the sum function of RORγt+ Tregs in glomerulonephritis (GN) remains unknown, we studied the effects of their absence. Purified CD4+ T cell populations, containing or lacking RORγt+ Tregs, were transferred into immunocompromised RAG1 knockout mice and the nephrotoxic nephritis model of GN was induced. Absence of RORγt+ Tregs significantly aggravated kidney injury, demonstrating overall kidney-protective properties. Analyses of immune responses showed, that RORγt+ Tregs were broadly immunosuppressive with no preference for a particular type of T cell response. Further characterization revealed a distinct functional and transcriptional profile, including enhanced production of IL-10. Expression of the chemokine receptor CCR6 marked a particularly potent subset, whose absence significantly worsened GN. As an underlying mechanism, we found that chemokine CCL20 acting through receptor CCR6 signaling mediated expansion and activation of RORγt+ Tregs. Finally, we also detected an increase of CCR6+ Tregs in kidney biopsies, as well as enhanced secretion of chemokine CCL20 in 21 patients with anti-neutrophil cytoplasmic antibody associated GN compared to that of 31 healthy living donors, indicating clinical relevance. Thus, our data characterize RORγt+ Tregs as anti-inflammatory mediators of GN and identify them as promising target for Treg directed therapies.

U2 - 10.1016/j.kint.2023.02.027

DO - 10.1016/j.kint.2023.02.027

M3 - SCORING: Journal article

C2 - 36924892

VL - 104

SP - 74

EP - 89

JO - KIDNEY INT

JF - KIDNEY INT

SN - 0085-2538

IS - 1

ER -