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Interleukin-23-Dependent γ/δ T Cells Produce Interleukin-17 and Accumulate in the Enthesis, Aortic Valve, and Ciliary Body in Mice

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Interleukin-23-Dependent γ/δ T Cells Produce Interleukin-17 and Accumulate in the Enthesis, Aortic Valve, and Ciliary Body in Mice. / Reinhardt, Annika; Yevsa, Tetyana; Worbs, Tim; Lienenklaus, Stefan; Sandrock, Inga; Oberdörfer, Linda; Korn, Thomas; Weiss, Siegfried; Förster, Reinhold; Prinz, Immo.

In: ARTHRITIS RHEUMATOL, Vol. 68, No. 10, 10.2016, p. 2476-86.

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

Harvard

Reinhardt, A, Yevsa, T, Worbs, T, Lienenklaus, S, Sandrock, I, Oberdörfer, L, Korn, T, Weiss, S, Förster, R & Prinz, I 2016, 'Interleukin-23-Dependent γ/δ T Cells Produce Interleukin-17 and Accumulate in the Enthesis, Aortic Valve, and Ciliary Body in Mice', ARTHRITIS RHEUMATOL, vol. 68, no. 10, pp. 2476-86. https://doi.org/10.1002/art.39732

APA

Reinhardt, A., Yevsa, T., Worbs, T., Lienenklaus, S., Sandrock, I., Oberdörfer, L., Korn, T., Weiss, S., Förster, R., & Prinz, I. (2016). Interleukin-23-Dependent γ/δ T Cells Produce Interleukin-17 and Accumulate in the Enthesis, Aortic Valve, and Ciliary Body in Mice. ARTHRITIS RHEUMATOL, 68(10), 2476-86. https://doi.org/10.1002/art.39732

Vancouver

Reinhardt A, Yevsa T, Worbs T, Lienenklaus S, Sandrock I, Oberdörfer L et al. Interleukin-23-Dependent γ/δ T Cells Produce Interleukin-17 and Accumulate in the Enthesis, Aortic Valve, and Ciliary Body in Mice. ARTHRITIS RHEUMATOL. 2016 Oct;68(10):2476-86. https://doi.org/10.1002/art.39732

Bibtex

@article{796c33d47dfa4286a07bdc1de5000729,
title = "Interleukin-23-Dependent γ/δ T Cells Produce Interleukin-17 and Accumulate in the Enthesis, Aortic Valve, and Ciliary Body in Mice",
abstract = "OBJECTIVE: The spondyloarthritides (SpA) are a group of rheumatic diseases characterized by ossification and inflammation of entheseal tissue, the region where tendon attaches to bone. Interleukin-23 (IL-23) is involved in the pathogenesis of SpA by acting on IL-23 receptor (IL-23R) expressed on enthesis-resident lymphocytes. Upon IL-23 binding, CD3+CD4-CD8- tissue-resident lymphocytes secrete IL-17A and IL-22, leading to inflammation, bone loss, and ossification. Knowledge about enthesis-resident lymphocytes remains fragmentary, and the contribution of entheseal γ/δ T cells in particular is not clear. This study was undertaken to investigate the presence of γ/δ T cells in the enthesis.METHODS: We used 2-photon microscopy and flow cytometry to analyze entheseal lymphocytes from C57BL/6, Tcrd-H2BeGFP, Rorc-GFP, and IL-23R-eGFP mice. To analyze entheseal γ/δ T cells in IL-23-induced inflammation, Tcrd-H2BeGFP mice were crossed with mice of the susceptible B10.RIII background. Hydrodynamic injection of IL-23 minicircle DNA was performed for overexpression of IL-23 and induction of inflammation. Light-sheet fluorescence microscopy was used to visualize arthritic inflammation.RESULTS: Activated Vγ6+CD27- γ/δ T cells were abundant in uninflamed entheseal tissue and constituted the large majority of retinoic acid receptor-related orphan nuclear receptor γt (RORγt)+IL-23R+ enthesis-resident lymphocytes. Fetal thymus-dependent γ/δ T cells were the main source of IL-17A at the enthesis. Under inflammatory conditions, γ/δ T cells increased in number at the Achilles tendon enthesis, aortic root, and adjacent to the ciliary body.CONCLUSION: Entheseal γ/δ T cells are derived from fetal thymus and are maintained as self-renewing tissue-resident cells. As main IL-17A producers within tissues exposed to mechanical stress including enthesis, γ/δ T cells are key players in the pathogenesis of IL-23-induced local inflammation.",
keywords = "Achilles Tendon/immunology, Animals, Ankle Joint/immunology, Aortic Valve/immunology, Ciliary Body/immunology, Enthesopathy/immunology, Flow Cytometry, Green Fluorescent Proteins/genetics, Interleukin-17/immunology, Interleukin-23/immunology, Interleukins/immunology, Mice, Mice, Transgenic, Microscopy, Fluorescence, Nuclear Receptor Subfamily 1, Group F, Member 3/immunology, Receptors, Antigen, T-Cell, gamma-delta/immunology, Spondylarthropathies/immunology, T-Lymphocyte Subsets/immunology, X-Ray Microtomography",
author = "Annika Reinhardt and Tetyana Yevsa and Tim Worbs and Stefan Lienenklaus and Inga Sandrock and Linda Oberd{\"o}rfer and Thomas Korn and Siegfried Weiss and Reinhold F{\"o}rster and Immo Prinz",
note = "{\textcopyright} 2016, American College of Rheumatology.",
year = "2016",
month = oct,
doi = "10.1002/art.39732",
language = "English",
volume = "68",
pages = "2476--86",
journal = "ARTHRITIS RHEUMATOL",
issn = "2326-5191",
publisher = "John Wiley and Sons Ltd",
number = "10",

}

RIS

TY - JOUR

T1 - Interleukin-23-Dependent γ/δ T Cells Produce Interleukin-17 and Accumulate in the Enthesis, Aortic Valve, and Ciliary Body in Mice

AU - Reinhardt, Annika

AU - Yevsa, Tetyana

AU - Worbs, Tim

AU - Lienenklaus, Stefan

AU - Sandrock, Inga

AU - Oberdörfer, Linda

AU - Korn, Thomas

AU - Weiss, Siegfried

AU - Förster, Reinhold

AU - Prinz, Immo

N1 - © 2016, American College of Rheumatology.

PY - 2016/10

Y1 - 2016/10

N2 - OBJECTIVE: The spondyloarthritides (SpA) are a group of rheumatic diseases characterized by ossification and inflammation of entheseal tissue, the region where tendon attaches to bone. Interleukin-23 (IL-23) is involved in the pathogenesis of SpA by acting on IL-23 receptor (IL-23R) expressed on enthesis-resident lymphocytes. Upon IL-23 binding, CD3+CD4-CD8- tissue-resident lymphocytes secrete IL-17A and IL-22, leading to inflammation, bone loss, and ossification. Knowledge about enthesis-resident lymphocytes remains fragmentary, and the contribution of entheseal γ/δ T cells in particular is not clear. This study was undertaken to investigate the presence of γ/δ T cells in the enthesis.METHODS: We used 2-photon microscopy and flow cytometry to analyze entheseal lymphocytes from C57BL/6, Tcrd-H2BeGFP, Rorc-GFP, and IL-23R-eGFP mice. To analyze entheseal γ/δ T cells in IL-23-induced inflammation, Tcrd-H2BeGFP mice were crossed with mice of the susceptible B10.RIII background. Hydrodynamic injection of IL-23 minicircle DNA was performed for overexpression of IL-23 and induction of inflammation. Light-sheet fluorescence microscopy was used to visualize arthritic inflammation.RESULTS: Activated Vγ6+CD27- γ/δ T cells were abundant in uninflamed entheseal tissue and constituted the large majority of retinoic acid receptor-related orphan nuclear receptor γt (RORγt)+IL-23R+ enthesis-resident lymphocytes. Fetal thymus-dependent γ/δ T cells were the main source of IL-17A at the enthesis. Under inflammatory conditions, γ/δ T cells increased in number at the Achilles tendon enthesis, aortic root, and adjacent to the ciliary body.CONCLUSION: Entheseal γ/δ T cells are derived from fetal thymus and are maintained as self-renewing tissue-resident cells. As main IL-17A producers within tissues exposed to mechanical stress including enthesis, γ/δ T cells are key players in the pathogenesis of IL-23-induced local inflammation.

AB - OBJECTIVE: The spondyloarthritides (SpA) are a group of rheumatic diseases characterized by ossification and inflammation of entheseal tissue, the region where tendon attaches to bone. Interleukin-23 (IL-23) is involved in the pathogenesis of SpA by acting on IL-23 receptor (IL-23R) expressed on enthesis-resident lymphocytes. Upon IL-23 binding, CD3+CD4-CD8- tissue-resident lymphocytes secrete IL-17A and IL-22, leading to inflammation, bone loss, and ossification. Knowledge about enthesis-resident lymphocytes remains fragmentary, and the contribution of entheseal γ/δ T cells in particular is not clear. This study was undertaken to investigate the presence of γ/δ T cells in the enthesis.METHODS: We used 2-photon microscopy and flow cytometry to analyze entheseal lymphocytes from C57BL/6, Tcrd-H2BeGFP, Rorc-GFP, and IL-23R-eGFP mice. To analyze entheseal γ/δ T cells in IL-23-induced inflammation, Tcrd-H2BeGFP mice were crossed with mice of the susceptible B10.RIII background. Hydrodynamic injection of IL-23 minicircle DNA was performed for overexpression of IL-23 and induction of inflammation. Light-sheet fluorescence microscopy was used to visualize arthritic inflammation.RESULTS: Activated Vγ6+CD27- γ/δ T cells were abundant in uninflamed entheseal tissue and constituted the large majority of retinoic acid receptor-related orphan nuclear receptor γt (RORγt)+IL-23R+ enthesis-resident lymphocytes. Fetal thymus-dependent γ/δ T cells were the main source of IL-17A at the enthesis. Under inflammatory conditions, γ/δ T cells increased in number at the Achilles tendon enthesis, aortic root, and adjacent to the ciliary body.CONCLUSION: Entheseal γ/δ T cells are derived from fetal thymus and are maintained as self-renewing tissue-resident cells. As main IL-17A producers within tissues exposed to mechanical stress including enthesis, γ/δ T cells are key players in the pathogenesis of IL-23-induced local inflammation.

KW - Achilles Tendon/immunology

KW - Animals

KW - Ankle Joint/immunology

KW - Aortic Valve/immunology

KW - Ciliary Body/immunology

KW - Enthesopathy/immunology

KW - Flow Cytometry

KW - Green Fluorescent Proteins/genetics

KW - Interleukin-17/immunology

KW - Interleukin-23/immunology

KW - Interleukins/immunology

KW - Mice

KW - Mice, Transgenic

KW - Microscopy, Fluorescence

KW - Nuclear Receptor Subfamily 1, Group F, Member 3/immunology

KW - Receptors, Antigen, T-Cell, gamma-delta/immunology

KW - Spondylarthropathies/immunology

KW - T-Lymphocyte Subsets/immunology

KW - X-Ray Microtomography

U2 - 10.1002/art.39732

DO - 10.1002/art.39732

M3 - SCORING: Journal article

C2 - 27111864

VL - 68

SP - 2476

EP - 2486

JO - ARTHRITIS RHEUMATOL

JF - ARTHRITIS RHEUMATOL

SN - 2326-5191

IS - 10

ER -