title: Differential Requirements of TCR Signaling in Homeostatic Maintenance and Function of Dendritic Epidermal T Cells.
abstract: Dendritic epidermal T cells (DETCs) are generated exclusively in the fetal thymus and maintained in the skin epithelium throughout postnatal life of the mouse. DETCs have restricted antigenic specificity as a result of their exclusive usage of a canonical TCR. Although the importance of the TCR in DETC development has been well established, the exact role of TCR signaling in DETC homeostasis and function remains incompletely defined. In this study, we investigated TCR signaling in fully matured DETCs by lineage-restricted deletion of the Lat gene, an essential signaling molecule downstream of the TCR. We found that Lat deletion impaired TCR-dependent cytokine gene activation and the ability of DETCs to undergo proliferative expansion. However, linker for activation of T cells-deficient DETCs were able to maintain long-term population homeostasis, although with a reduced proliferation rate. Mice with Lat deletion in DETCs exhibited delayed wound healing accompanied by impaired clonal expansion within the wound area. Our study revealed differential requirements for TCR signaling in homeostatic maintenance of DETCs and in their effector function during wound healing.
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27710;
authors.forename: Baojun
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27710;
authors.forename: Jianxuan
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC 27710; and.
authors.forename: Yiqun
authors.initials: Y
authors.lastname: Jiao
authors.affiliation: Duke Cancer Institute, Duke University Medical Center, Durham, NC 27710.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Bock
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27710;
authors.forename: Meifang
authors.initials: M
authors.lastname: Dai
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC 27710; and.
authors.forename: Benny
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27710; Department of Medicine, Duke University Medical Center, Durham, NC 27710; and Duke Cancer Institute, Duke University Medical Center, Durham, NC 27710.
authors.forename: Nelson
authors.initials: N
authors.lastname: Chao
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27710; Duke Cancer Institute, Duke University Medical Center, Durham, NC 27710.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27710; Duke Cancer Institute, Duke University Medical Center, Durham, NC 27710 yzhuang@duke.edu.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhuang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D005434:Flow Cytometry; D006706:Homeostasis / Q000235:genetics / Q000276:immunology*; D007801:Langerhans Cells / Q000276:immunology* / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D010750:Phosphoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014945:Wound Healing / Q000235:genetics / Q000276:immunology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C491734:Lat protein, mouse; D008164:Luminescent Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; D011948:Receptors, Antigen, T-Cell