Keratinocytes enriched for epidermal stem cells differ in their response to IFN-gamma from other proliferative keratinocytes.
The epidermis has a pool of adult stem cells [epidermal stem cells (ESC)]. Although the localization of ESC is well described, we lack a clear understanding of their role in perturbed conditions such as inflammation. One of the most important mediators in inflammatory skin diseases acting on keratinocytes (KCs) is interferon gamma (IFN-gamma). The assumption that ESC might generate a protected niche prompted us to investigate their response to the pro-inflammatory cytokine IFN-gamma. In this study, we isolated two populations of KCs according to their adherence ability. ESC enriched by adherence showed a higher CD29 and CD49f expression compared with other KCs. Surprisingly, surface expression of CD54 was more inducible upon IFN-gamma stimulation in short-term cultures of the ESC subpopulation. In contrary to that, a markedly lower induction of IL-18 and reduced basal production of CCL2 were observable in ESC. No differences in IFN-gamma-induced interleukin (IL)-10, CXCL10, CCL22 or transforming growth factor (TGF)beta1 secretion were detectable between the two keratinocyte subpopulations. These results suggest that ESC respond to IFN-gamma with a 'restricted' pattern of pro-inflammatory cytokines, and do not build up an anti-inflammatory microenvironment by means of TGF-beta or IL-10. Activated ESC possess the capability to interact with infiltrating lymphocytes via CD54. In conclusion, the ESC compartment might actively contribute to the immunological properties of the skin organ.
Zeitvogel
Jana
J
Department of Dermatology, Hannover Medical School, Hannover, Germany.
Werfel
Thomas
T
Wittmann
Miriam
M
D053687:Adult Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D054422:Chemokine CCL22 / Q000235:genetics / Q000378:metabolism; D054357:Chemokine CXCL10 / Q000235:genetics / Q000378:metabolism; D000078404:Epidermal Cells; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D039503:Integrin alpha6 / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology*; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D020382:Interleukin-18 / Q000235:genetics / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
C111835:CCL2 protein, human; C515482:CCL22 protein, human; C114753:CXCL10 protein, human; D018932:Chemokine CCL2; D054422:Chemokine CCL22; D054357:Chemokine CXCL10; C508609:IL10 protein, human; D039503:Integrin alpha6; D019012:Integrin beta1; D020382:Interleukin-18; D053773:Transforming Growth Factor beta1; D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10; D007371:Interferon-gamma