Increased Production of IL-17A-Producing γδ T Cells in the Thymus of Filaggrin-Deficient Mice

Mia Hamilton Jee; Jeanne Duus Johansen; Terkild Brink Buus; Trine Hilkjær Petersen; Anne-Sofie Østergaard Gadsbøll; Anders Woetmann; Niels Ødum; Jacob Pontoppidan Thyssen; Andrea Jane White; Graham Anderson; Carsten Geisler; Charlotte Menné Bonefeld

doi:10.3389/fimmu.2018.00988

Increased Production of IL-17A-Producing γδ T Cells in the Thymus of Filaggrin-Deficient Mice

Mia Hamilton Jee, Jeanne Duus Johansen, Terkild Brink Buus, Trine Hilkjær Petersen, Anne-Sofie Østergaard Gadsbøll, Anders Woetmann, Niels Ødum, Jacob Pontoppidan Thyssen, Andrea Jane White, Graham Anderson, Carsten Geisler, Charlotte Menné Bonefeld

7 Citationer (Scopus)

Abstract

Mutations in the filaggrin gene (Flg) are associated with increased systemic levels of Th17 cells and increased IL-17A production following antigen exposure in both humans and mice. In addition to Th17 cells, γδ T cells can produce IL-17A. The differentiation of γδ T cells to either IFNγ or IL-17A-producing (γδT17) cells is mainly determined in the thymus. Interestingly, it has been reported that filaggrin is expressed in the Hassall bodies in the human thymic medulla. However, whether filaggrin affects γδ T cell development is not known. Here, we show that filaggrin-deficient flaky tail (ft/ft) mice have an increased number of γδT17 cells in the spleen, epidermis, and thymus compared to wild-type (WT) mice. We demonstrate that filaggrin is expressed in the mouse thymic medulla and that blocking the egress of cells from the thymus results in accumulation of Vγ2+ γδT17 cells in the thymus of adult ft/ft mice. Finally, we find increased T cell receptor expression levels on γδ T cells and increased levels of IL-6 and IL-23 in the thymus of ft/ft mice. These findings demonstrate that filaggrin is expressed in the mouse thymic medulla and that production of Vγ2+ γδT17 cells is dysregulated in filaggrin-deficient ft/ft mice.

Originalsprog	Engelsk
Artikelnummer	988
Tidsskrift	Frontiers in Immunology
Vol/bind	9
Sider (fra-til)	1-11
ISSN	1664-3224
DOI	https://doi.org/10.3389/fimmu.2018.00988
Status	Udgivet - 8 maj 2018

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10.3389/fimmu.2018.00988Licens: CC BY

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title = "Increased Production of IL-17A-Producing γδ T Cells in the Thymus of Filaggrin-Deficient Mice",

abstract = "Mutations in the filaggrin gene (Flg) are associated with increased systemic levels of Th17 cells and increased IL-17A production following antigen exposure in both humans and mice. In addition to Th17 cells, γδ T cells can produce IL-17A. The differentiation of γδ T cells to either IFNγ or IL-17A-producing (γδT17) cells is mainly determined in the thymus. Interestingly, it has been reported that filaggrin is expressed in the Hassall bodies in the human thymic medulla. However, whether filaggrin affects γδ T cell development is not known. Here, we show that filaggrin-deficient flaky tail (ft/ft) mice have an increased number of γδT17 cells in the spleen, epidermis, and thymus compared to wild-type (WT) mice. We demonstrate that filaggrin is expressed in the mouse thymic medulla and that blocking the egress of cells from the thymus results in accumulation of Vγ2+ γδT17 cells in the thymus of adult ft/ft mice. Finally, we find increased T cell receptor expression levels on γδ T cells and increased levels of IL-6 and IL-23 in the thymus of ft/ft mice. These findings demonstrate that filaggrin is expressed in the mouse thymic medulla and that production of Vγ2+ γδT17 cells is dysregulated in filaggrin-deficient ft/ft mice.",

author = "Jee, {Mia Hamilton} and Johansen, {Jeanne Duus} and Buus, {Terkild Brink} and Petersen, {Trine Hilkj{\ae}r} and Gadsb{\o}ll, {Anne-Sofie {\O}stergaard} and Anders Woetmann and Niels {\O}dum and Thyssen, {Jacob Pontoppidan} and White, {Andrea Jane} and Graham Anderson and Carsten Geisler and Bonefeld, {Charlotte Menn{\'e}}",

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T1 - Increased Production of IL-17A-Producing γδ T Cells in the Thymus of Filaggrin-Deficient Mice

AU - Jee, Mia Hamilton

AU - Johansen, Jeanne Duus

AU - Buus, Terkild Brink

AU - Petersen, Trine Hilkjær

AU - Gadsbøll, Anne-Sofie Østergaard

AU - Woetmann, Anders

AU - Ødum, Niels

AU - Thyssen, Jacob Pontoppidan

AU - White, Andrea Jane

AU - Anderson, Graham

AU - Geisler, Carsten

AU - Bonefeld, Charlotte Menné

PY - 2018/5/8

Y1 - 2018/5/8

N2 - Mutations in the filaggrin gene (Flg) are associated with increased systemic levels of Th17 cells and increased IL-17A production following antigen exposure in both humans and mice. In addition to Th17 cells, γδ T cells can produce IL-17A. The differentiation of γδ T cells to either IFNγ or IL-17A-producing (γδT17) cells is mainly determined in the thymus. Interestingly, it has been reported that filaggrin is expressed in the Hassall bodies in the human thymic medulla. However, whether filaggrin affects γδ T cell development is not known. Here, we show that filaggrin-deficient flaky tail (ft/ft) mice have an increased number of γδT17 cells in the spleen, epidermis, and thymus compared to wild-type (WT) mice. We demonstrate that filaggrin is expressed in the mouse thymic medulla and that blocking the egress of cells from the thymus results in accumulation of Vγ2+ γδT17 cells in the thymus of adult ft/ft mice. Finally, we find increased T cell receptor expression levels on γδ T cells and increased levels of IL-6 and IL-23 in the thymus of ft/ft mice. These findings demonstrate that filaggrin is expressed in the mouse thymic medulla and that production of Vγ2+ γδT17 cells is dysregulated in filaggrin-deficient ft/ft mice.

AB - Mutations in the filaggrin gene (Flg) are associated with increased systemic levels of Th17 cells and increased IL-17A production following antigen exposure in both humans and mice. In addition to Th17 cells, γδ T cells can produce IL-17A. The differentiation of γδ T cells to either IFNγ or IL-17A-producing (γδT17) cells is mainly determined in the thymus. Interestingly, it has been reported that filaggrin is expressed in the Hassall bodies in the human thymic medulla. However, whether filaggrin affects γδ T cell development is not known. Here, we show that filaggrin-deficient flaky tail (ft/ft) mice have an increased number of γδT17 cells in the spleen, epidermis, and thymus compared to wild-type (WT) mice. We demonstrate that filaggrin is expressed in the mouse thymic medulla and that blocking the egress of cells from the thymus results in accumulation of Vγ2+ γδT17 cells in the thymus of adult ft/ft mice. Finally, we find increased T cell receptor expression levels on γδ T cells and increased levels of IL-6 and IL-23 in the thymus of ft/ft mice. These findings demonstrate that filaggrin is expressed in the mouse thymic medulla and that production of Vγ2+ γδT17 cells is dysregulated in filaggrin-deficient ft/ft mice.

U2 - 10.3389/fimmu.2018.00988

DO - 10.3389/fimmu.2018.00988

M3 - Journal article

C2 - 29867965

SN - 1664-3224

VL - 9

SP - 1

EP - 11

JO - Frontiers in Immunology

JF - Frontiers in Immunology

M1 - 988

ER -

Increased Production of IL-17A-Producing γδ T Cells in the Thymus of Filaggrin-Deficient Mice

Abstract

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