title: Differential developmental requirement and peripheral regulation for dermal Vγ4 and Vγ6T17 cells in health and inflammation.
abstract: Dermal IL-17-producing γδT cells have a critical role in skin inflammation. However, their development and peripheral regulation have not been fully elucidated. Here we demonstrate that dermal γδT cells develop from the embryonic thymus and undergo homeostatic proliferation after birth with diversified TCR repertoire. Vγ6T cells are bona fide resident, but precursors of dermal Vγ4T cells may require extrathymic environment for imprinting skin-homing properties. Thymic Vγ6T cells are more competitive than Vγ4 for dermal γδT cell reconstitution and TCRδ(-/-) mice reconstituted with Vγ6 develop psoriasis-like inflammation after IMQ-application. Although both IL-23 and IL-1β promote Vγ4 and Vγ6 proliferation, Vγ4 are the main source of IL-17 production that requires IL-1 signalling. Mice with deficiency of IL-1RI signalling have significantly decreased skin inflammation. These studies reveal a differential developmental requirement and peripheral regulation for dermal Vγ6 and Vγ4 γδT cells, implying a new mechanism that may be involved in skin inflammation.
authors.affiliation: 1] James Graham Brown Cancer Center, Department of Medicine and Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky 40202, USA [2].
authors.forename: Yihua
authors.initials: Y
authors.lastname: Cai
authors.affiliation: 1] Department of Dermatology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200025, China [2].
authors.forename: Feng
authors.initials: F
authors.lastname: Xue
authors.affiliation: James Graham Brown Cancer Center, Department of Medicine and Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky 40202, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Fleming
authors.affiliation: Center for Molecular Immunology and Infectious Diseases and Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, Pennsylvania 16802, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.affiliation: James Graham Brown Cancer Center, Department of Medicine and Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky 40202, USA.
authors.forename: Chuanlin
authors.initials: C
authors.lastname: Ding
authors.affiliation: James Graham Brown Cancer Center, Department of Medicine and Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky 40202, USA.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Ma
authors.affiliation: James Graham Brown Cancer Center, Department of Medicine and Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky 40202, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.affiliation: James Graham Brown Cancer Center, Department of Medicine and Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky 40202, USA.
authors.forename: Huang-ge
authors.initials: HG
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200025, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Center for Molecular Immunology and Infectious Diseases and Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, Pennsylvania 16802, USA.
authors.forename: Na
authors.initials: N
authors.lastname: Xiong
authors.affiliation: James Graham Brown Cancer Center, Department of Medicine and Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky 40202, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Yan
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D007249:Inflammation / Q000378:metabolism*; D007375:Interleukin-1 / Q000378:metabolism; D020381:Interleukin-17 / Q000096:biosynthesis / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D012867:Skin / Q000166:cytology / Q000378:metabolism*
chemical_list: D007375:Interleukin-1; D020381:Interleukin-17; D016692:Receptors, Antigen, T-Cell, gamma-delta