TY - JOUR
T1 - Langerhans cells favor skin flora tolerance through limited presentation of bacterial antigens and induction of regulatory T cells
AU - van der Aar, Angelic M. G.
AU - Picavet, Daisy I.
AU - Muller, Femke J.
AU - de Boer, Leonie
AU - van Capel, Toni M. M.
AU - Zaat, Sebastian A. J.
AU - Bos, Jan D.
AU - Janssen, Hans
AU - George, Thaddeus C.
AU - Kapsenberg, Martien L.
AU - van Ham, S. Marieke
AU - Teunissen, Marcel B. M.
AU - de Jong, Esther C.
PY - 2013
Y1 - 2013
N2 - 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
AB - 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
U2 - https://doi.org/10.1038/jid.2012.500
DO - https://doi.org/10.1038/jid.2012.500
M3 - Article
C2 - 23389393
SN - 0022-202X
VL - 133
SP - 1240
EP - 1249
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 5
ER -