title: Stromal cells control the epithelial residence of DCs and memory T cells by regulated activation of TGF-β.
abstract: Cells of the immune system that reside in barrier epithelia provide a first line of defense against pathogens. Langerhans cells (LCs) and CD8(+) tissue-resident memory T cells (TRM cells) require active transforming growth factor-β1 (TGF-β) for epidermal residence. Here we found that integrins αvβ6 and αvβ8 were expressed in non-overlapping patterns by keratinocytes (KCs) and maintained the epidermal residence of LCs and TRM cells by activating latent TGF-β. Similarly, the residence of dendritic cells and TRM cells in the small intestine epithelium also required αvβ6. Treatment of the skin with ultraviolet irradiation decreased integrin expression on KCs and reduced the availability of active TGF-β, which resulted in LC migration. Our data demonstrated that regulated activation of TGF-β by stromal cells was able to directly control epithelial residence of cells of the immune system through a novel mechanism of intercellular communication.
authors.affiliation: Department of Dermatology, Center for Immunology, University of Minnesota, Minneapolis, Minnesota USA.
authors.forename: Javed
authors.initials: J
authors.lastname: Mohammed
authors.affiliation: Department of Microbiology and Immunology, Center for Immunology, University of Minnesota, Minneapolis, Minnesota USA.
authors.forename: Lalit K
authors.identifier: http://orcid.org/0000-0002-8597-3949
authors.initials: LK
authors.lastname: Beura
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Aleh
authors.initials: A
authors.lastname: Bobr
authors.affiliation: Department of Dermatology, Center for Immunology, University of Minnesota, Minneapolis, Minnesota USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Astry
authors.affiliation: Department of Dermatology, Center for Immunology, University of Minnesota, Minneapolis, Minnesota USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Chicoine
authors.affiliation: Department of Dermatology, Center for Immunology, University of Minnesota, Minneapolis, Minnesota USA.
authors.forename: Sakeen W
authors.initials: SW
authors.lastname: Kashem
authors.affiliation: Department of Dermatology, Center for Immunology, University of Minnesota, Minneapolis, Minnesota USA.
authors.forename: Nathan E
authors.initials: NE
authors.lastname: Welty
authors.affiliation: Department of Dermatology, Center for Immunology, University of Minnesota, Minneapolis, Minnesota USA.
authors.forename: Botond Z
authors.initials: BZ
authors.lastname: Igyártó
authors.affiliation: Department of Dermatology, Center for Immunology, University of Minnesota, Minneapolis, Minnesota USA.
authors.forename: Sathi
authors.initials: S
authors.lastname: Wijeyesinghe
authors.affiliation: Department of Microbiology and Immunology, Center for Immunology, University of Minnesota, Minneapolis, Minnesota USA.
authors.forename: Emily A
authors.initials: EA
authors.lastname: Thompson
authors.affiliation: Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.|Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Matte
authors.affiliation: Centre de Recherche en Cancérologie de Lyon, INSERM U1052, CNRS UMR5286, Lyon, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Bartholin
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: Alesia
authors.initials: A
authors.lastname: Kaplan
authors.affiliation: Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Dean
authors.identifier: http://orcid.org/0000-0002-6277-2036
authors.initials: D
authors.lastname: Sheppard
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Alina G
authors.initials: AG
authors.lastname: Bridges
authors.affiliation: Department of Medicine, University of Pittsburgh Cancer Center Institute, Pittsburgh, Pennsylvania, USA.|Department of Immunology, University of Pittsburgh Cancer Center Institute, Pittsburgh, Pennsylvania, USA.
authors.forename: Warren D
authors.initials: WD
authors.lastname: Shlomchik
authors.affiliation: Department of Microbiology and Immunology, Center for Immunology, University of Minnesota, Minneapolis, Minnesota USA.
authors.forename: David
authors.initials: D
authors.lastname: Masopust
authors.affiliation: Department of Dermatology, Center for Immunology, University of Minnesota, Minneapolis, Minnesota USA.|Department of Dermatology, University of Pittsburgh, Pennsylvania, USA.|Department of Immunology, University of Pittsburgh, Pennsylvania, USA.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Kaplan
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002465:Cell Movement; D000078404:Epidermal Cells; D004817:Epidermis / Q000276:immunology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D018928:Immunity, Mucosal; D016023:Integrins / Q000276:immunology; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology*; D007421:Intestine, Small / Q000166:cytology / Q000276:immunology; D015603:Keratinocytes / Q000276:immunology*; D007801:Langerhans Cells / Q000166:cytology / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D008907:Mink; D016133:Polymerase Chain Reaction; D017154:Stromal Cells; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000276:immunology*; D053773:Transforming Growth Factor beta1 / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D016023:Integrins; C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C073878:integrin alphavbeta6; C403414:integrin alphavbeta8