title: TIM-4 is differentially expressed in the distinct subsets of dendritic cells in skin and skin-draining lymph nodes and controls skin Langerhans cell homeostasis.
abstract: T cell immunoglobulin and mucin-4 (TIM-4), mainly expressed on dendritic cells (DC) and macrophages, plays an essential role in regulating immune responses. Langerhans cells (LC), which are the sole DC subpopulation residing at the epidermis, are potent mediators of immune surveillance and tolerance. However, the significance of TIM-4 on epidermal LCs, along with other cutaneous DCs, remains totally unexplored. For the first time, we discovered that epidermal LCs expressed TIM-4 and displayed an increased level of TIM-4 expression upon migration. We also found that dermal CD207+ DCs and lymph node (LN) resident CD207-CD4+ DCs highly expressed TIM-4, while dermal CD207- DCs and LN CD207-CD4- DCs had limited TIM-4 expressions. Using TIM-4-deficient mice, we further demonstrated that loss of TIM-4 significantly upregulated the frequencies of epidermal LCs and LN resident CD207-CD4+ DCs. In spite of this, the epidermal LCs of TIM-4-deficient mice displayed normal phagocytic and migratory abilities, comparable maturation status upon the stimulation as well as normal repopulation under the inflamed state. Moreover, lack of TIM-4 did not affect dinitrofluorobenzene-induced contact hypersensitivity response. In conclusion, our results indicated that TIM-4 was differentially expressed in the distinct subsets of DCs in skin and skin-draining LNs, and specifically regulated epidermal LC and LN CD207-CD4+ DC homeostasis.
authors.affiliation: Department of Dermatology, Second Military Medical University Changhai Hospital, Shanghai, China.|Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI, United States of America.|Department of Dermatology, Henry Ford Health System, Detroit, MI, United States of America.
authors.forename: Xilin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI, United States of America.|Department of Dermatology, Henry Ford Health System, Detroit, MI, United States of America.
authors.forename: Queping
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI, United States of America.|Department of Dermatology, Henry Ford Health System, Detroit, MI, United States of America.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.affiliation: Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI, United States of America.|Department of Dermatology, Henry Ford Health System, Detroit, MI, United States of America.
authors.forename: Guihua
authors.initials: G
authors.lastname: Li
authors.affiliation: Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI, United States of America.|Department of Dermatology, Henry Ford Health System, Detroit, MI, United States of America.
authors.forename: Matthew
authors.initials: M
authors.lastname: Weiland
authors.affiliation: Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI, United States of America.
authors.forename: Fu-Shin
authors.initials: FS
authors.lastname: Yu
authors.affiliation: Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI, United States of America.|Department of Dermatology, Henry Ford Health System, Detroit, MI, United States of America.|Department of Internal Medicine, Henry Ford Health System, Detroit, MI, United States of America.
authors.forename: Qing-Sheng
authors.initials: QS
authors.lastname: Mi
authors.affiliation: Department of Dermatology, Second Military Medical University Changhai Hospital, Shanghai, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Gu
authors.affiliation: Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI, United States of America.|Department of Dermatology, Henry Ford Health System, Detroit, MI, United States of America.|Department of Internal Medicine, Henry Ford Health System, Detroit, MI, United States of America.
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D006706:Homeostasis; D007801:Langerhans Cells / Q000166:cytology / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology*; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012867:Skin / Q000166:cytology / Q000276:immunology*
chemical_list: D008565:Membrane Proteins; C500399:TIM-4 protein, mouse
keywords: Immune response; Immunity; Immunology and Microbiology Section; Langerhans cells; TIM-4; dendritic cells; skin; skin-draining lymph node