Stromal cells control the epithelial residence of DCs and memory T cells by regulated activation of TGF-β

• DOI: 10.1038/ni.3396
• Publication Date: 2016-02-22T16:12:18Z
• Authors: Javed Mohammed; Lalit K Beura; Aleh Bobr; Brian Astry; Brian Chicoine; Sakeen W Kashem; Nathan E Welty; Botond Z Igyártó; Sathi Wijeyesinghe; Emily A Thompson; Catherine Matte; Laurent Bartholin; Alesia Kaplan; Dean Sheppard; Alina G Bridges; Warren D Shlomchik; David Masopust; Daniel H Kaplan
• Keywords: Keratinocytes; Integrins; T-Lymphocytes; Fluorescent Antibody Technique; Growth; CD8-Positive T-Lymphocytes; Small; Polymerase Chain Reaction; Epithelium; immunology; Mice; 0302 clinical medicine; T-Lymphocyte Subsets; Transforming Growth Factor beta; Cell Movement; Intestine, Small; Intestinal Mucosa; Skin; Mice, Knockout; Mucosal; Flow Cytometry; Intestine; 3. Good health; Medicine; France; 1.1 Normal biological development and functioning; Knockout; Cells; Immunology; [SDV.CAN]Life Sciences [q-bio]/Cancer; Dermatology; Transforming Growth Factor beta1; 03 medical and health sciences; [SDV.CAN] Life Sciences [q-bio]/Cancer; Antigens, Neoplasm; Animals; Humans; Antigens; Immunity, Mucosal; Biomedical and Clinical Sciences; Inflammatory and immune system; microbiology; Immunity; Dendritic Cells; Epidermal Cells; Mink; Biochemistry and cell biology; Immune System; Langerhans Cells; Neoplasm; pathology; Epidermis; Stromal Cells; Laboratories

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.