Epidermal gammadelta T cells sense precancerous cellular dysregulation and initiate immune responses.
Hyperplasia associated with a loss of tissue homeostasis can induce DNA replication stress, leading to precancerous dysregulation. Epidermal gammadelta T cells reside in the primary barrier that protects against diverse environmental insults; however, the functions of these T cells in tissue surveillance are not completely understood. In mice with inducible Notch1 inactivation in keratinocytes that causes epidermal hyperplasia, epidermal gammadelta T cells sensed stressed keratinocytes and migrated into the cutaneous draining lymph nodes. Simultaneous induction of beta-galactosidase (beta-Gal) as a putative antigen expressed in the process of precancerous dysregulation and Notch1 ablation in the epidermis resulted in elevated beta-Gal-specific IgG2a production. Epidermal gammadelta T cells were found to have the capacity to express chemokine (C-C motif) receptor 7 and migrate into the lymph nodes. Cutaneous draining lymph node cells in Notch1-inactivated mice expressed high levels of IFN-gamma upon anti-CD3 plus anti-CD28 stimulation. Furthermore, induced expression of beta-Gal in mice that lacked epidermal gammadelta T cells failed to induce anti-beta-Gal IgG. These results suggest that epidermal gammadelta T cells play an essential role in the initiation process of epidermal antigen-specific humoral immune responses and demonstrate the importance of epidermal gammadelta T cells in sensing precancerous dysregulation and activating adaptive immunity.
Shimura
Eri
E
Research Institute for Biological Sciences, Tokyo University of Science, 2669, Yamazaki, Noda, Chiba 278-0022, Japan.
Hozumi
Nobumichi
N
Kanagawa
Osami
O
Metzger
Daniel
D
Chambon
Pierre
P
Radtke
Freddy
F
Hirose
Sachiko
S
Nakano
Naoko
N
D000818:Animals; D000918:Antibody Specificity; D001402:B-Lymphocytes / Q000276:immunology; D002465:Cell Movement; D004817:Epidermis / Q000276:immunology* / Q000473:pathology; D007074:Immunoglobulin G / Q000276:immunology; D015603:Keratinocytes / Q000276:immunology / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011230:Precancerous Conditions / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D051881:Receptor, Notch1 / Q000235:genetics; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D054400:Receptors, CCR7 / Q000096:biosynthesis; D012878:Skin Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D001616:beta-Galactosidase / Q000235:genetics
D007074:Immunoglobulin G; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D016692:Receptors, Antigen, T-Cell, gamma-delta; D054400:Receptors, CCR7; D001616:beta-Galactosidase