CCR10 regulates balanced maintenance and function of resident regulatory and effector T cells to promote immune homeostasis in the skin.
BACKGROUND
CCR10 and CCL27 make up the most skin-specific chemokine receptor/ligand pair implicated in skin allergy and inflammatory diseases, including atopic dermatitis and psoriasis. This pair is thought to regulate the migration, maintenance, or both of skin T cells and is suggested to be therapeutic targets for treatment of skin diseases. However, the functional importance of CCR10/CCL27 in vivo remains elusive.


OBJECTIVE
We sought to determine the expression and function of CCR10 in different subsets of skin T cells under both homeostatic and inflammatory conditions to gain a mechanistic insight into the potential roles of CCR10 during skin inflammation.


METHODS
Using heterozygous and homozygous CCR10 knockout/enhanced green fluorescent protein knockin mice, we assessed the expression of CCR10 on regulatory and effector T cells of healthy and inflamed skin induced by chemicals, pathogens, and autoreactive T cells. In addition, we assessed the effect of CCR10 knockout on the maintenance and functions of different T cells and inflammatory status in the skin during different phases of the immune response.


RESULTS
CCR10 expression is preferentially induced on memory-like skin-resident T cells and their progenitors for their maintenance in homeostatic skin but not expressed on most skin-infiltrating effector T cells during inflammation. In CCR10 knockout mice the imbalanced presence and dysregulated function of resident regulatory and effector T cells result in over-reactive and prolonged innate and memory responses in the skin, leading to increased clearance of Leishmania species infection in the skin.


CONCLUSIONS
CCR10 is a critical regulator of skin immune homeostasis.
Centre for Molecular Immunology and Infectious Disease, Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, Pa.
Mingcan
M
Xia
Centre for Molecular Immunology and Infectious Disease, Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, Pa.
Shaomin
S
Hu
Centre for Molecular Immunology and Infectious Disease, Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, Pa.
Yaoyao
Y
Fu
Teaching and Research Section of Nuclear Medicine, Anhui Medical University, Anhui, China.
Wensen
W
Jin
Teaching and Research Section of Nuclear Medicine, Anhui Medical University, Anhui, China.
Qiyi
Q
Yi
Cell and Development Biology Graduate Program, Pennsylvania State University, University Park, Pa.
Yurika
Y
Matsui
Centre for Molecular Immunology and Infectious Disease, Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, Pa.
Jie
J
Yang
Eck Institute for Global Health, Department of Biological Sciences, University of Notre Dame, Notre Dame, Ind.
Mary Ann
MA
McDowell
Centre for Molecular Immunology and Infectious Disease, Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, Pa.
Surojit
S
Sarkar
Centre for Molecular Immunology and Infectious Disease, Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, Pa.
Vandana
V
Kalia
Centre for Molecular Immunology and Infectious Disease, Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, Pa. Electronic address: nux1@psu.edu.
Na
N
Xiong
D000818:Animals; D015551:Autoimmunity / Q000235:genetics; D002478:Cells, Cultured; D054425:Chemokine CCL27 / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000276:immunology*; D006706:Homeostasis; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007156:Immunologic Memory; D007249:Inflammation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009928:Organ Specificity; D011565:Psoriasis / Q000276:immunology*; D054447:Receptors, CCR10 / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D015854:Up-Regulation
C515707:Ccr10 protein, mouse; D054425:Chemokine CCL27; D054447:Receptors, CCR10
Chemokine receptor CCR10; Leishmania species; allergy; dermatitis; immune homeostasis; inflammation; maintenance; migration; regulatory T cells; skin infection; skin-resident T cells