title: Langerhans cells favor skin flora tolerance through limited presentation of bacterial antigens and induction of regulatory T cells.
abstract: The mechanisms preventing detrimental T-cell responses against commensal skin bacteria remain elusive. Using monocyte-derived and skin-derived dendritic cells (DCs), we demonstrate that epidermal Langerhans cells (LCs), the DCs in the most superficial layer of the skin, have a poor capacity to internalize bacteria because of low expression of FcγRIIa. Furthermore, LCs show deficiency in processing and major histocompatibility complex II (MHC-II)-restricted presentation of bacterial antigens, as a result of a decreased expression of molecules involved in these functionalities. The reduced capacity to take up, process, and present bacterial antigens cannot be restored by LC activation by ectopically expressed Toll-like receptors or by cytokines. Consequently, bacteria-primed LCs poorly restimulate antibacterial memory CD4(+) T cells and inefficiently induce bacteria-specific effector CD4(+) T cells from naive T cells; however, they initiate the development of regulatory Foxp3(+)CD4(+) T cells, which are able to suppress the proliferation of autologous bystander T cells specific for the same bacteria. In contrast, dermal DCs that reside in the deeper dermal layer of the skin efficiently present bacterial antigens and provoke robust antibacterial naive and memory CD4(+) T-cell responses. In conclusion, LCs form a unique DC subset that is adapted at multiple levels for the maintenance of tolerance to bacterial skin flora.
authors: Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors: Angelic M G
authors: AM
authors: van der Aar
authors: Daisy I
authors: DI
authors: Picavet
authors: Femke J
authors: FJ
authors: Muller
authors: Leonie
authors: L
authors: de Boer
authors: Toni M M
authors: TM
authors: van Capel
authors: Sebastian A J
authors: SA
authors: Zaat
authors: Jan D
authors: JD
authors: Bos
authors: Hans
authors: H
authors: Janssen
authors: Thaddeus C
authors: TC
authors: George
authors: Martien L
authors: ML
authors: Kapsenberg
authors: S Marieke
authors: SM
authors: van Ham
authors: Marcel B M
authors: MB
authors: Teunissen
authors: Esther C
authors: EC
authors: de Jong
mesh_terms: D000942:Antigens, Bacterial / Q000378:metabolism*; D015704:CD4 Antigens / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology*; D007111:Immunity, Cellular; D007801:Langerhans Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D017452:Receptors, IgG / Q000378:metabolism; D012867:Skin / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D015704:CD4 Antigens; C445323:FCGR2A protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D017452:Receptors, IgG; D051193:Toll-Like Receptors