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.
Department of Dermatology, Hannover Medical School, Hannover, Germany.
Jana
J
Zeitvogel
Thomas
T
Werfel
Miriam
M
Wittmann
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