Sebum lipids influence macrophage polarization and activation

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Sebocytes contribute to skin inflammation by promoting the differentiation of Th17 cells

BACKGROUND: The main function of sebocytes is considered to be the lipid production for moisturizing the skin. However, it became recently apparent that sebocytes release chemokines and cytokines and respond to pro-inflammatory stimuli as well as presence of bacteria. OBJECTIVES: To analyze the functional communication between human sebocytes and T cells. METHODS: Immunofluorescence stainings for CD4 and IL-17 were performed on acne sections and healthy skin. Migration assays and T cell stimulation cultures were performed with supernatants derived from unstimulated or pre-stimulated SZ95 sebocytes. DCs were generated in presence of SZ95 supernatant and subsequently used in mixed leukocyte reactions. RESULTS: We could show that CD4+IL-17+ T cells accumulate around the pilosebaceous unit and are in close contact with sebocytes in acne lesions. By using SZ95 sebocyte supernatant, we demonstrate a chemotactic effect of sebocytes on neutrophils, monocytes and T cells in a CXCL-8 dependent manner. Furthermore, sebocyte supernatant induces the differentiation of CD4+ CD45RA+ naive T cells into Th17 cells via the secretion of IL-6, TGF-beta and, most importantly, IL-1beta. No direct effects of sebocytes on the function of CD4+ CD45RO+ memory T cells were detected. Moreover, sebocytes functionally interact with Propionibacterium acnes in the maturation of dendritic cells leading to antigen presenting cells that preferentially prime Th17 cells. CONCLUSIONS: Our study provides evidence that human sebocytes actively participate in inflammatory processes in the skin by recruiting and communicating with immune cells. This interaction leads to the generation of Th17 cells that might contribute not only to the pathogenesis of acne vulgaris, but to several inflammatory skin diseases. This article is protected by copyright. All rights reserved

Sebum lipids influence macrophage polarization and activation

BACKGROUND: As lipids are known to regulate macrophage functions it is reasonable to suppose that a sebocyte - macrophage axis mediated by sebum lipids may exist. OBJECTIVE: To investigate if sebocytes could contribute to the differentiation, polarization and function of macrophages with their secreted lipids. METHODS: Oil-red-O lipid staining and Raman spectroscopy were used to assess the dermal lipid content and penetration. Immunohistochemistry was used to analyse the macrophage subsets. Human peripheral blood monocytes were differentiated in the presence of either supernatant from human SZ95 sebocytes or major sebum lipid components and activated with Propionibacterium acnes. Macrophage surface markers and their capacity to uptake FITC-Propionibacterium acnes were detected by FACS measurements. Cytokine protein levels were evaluated by ELISA and Western blot analysis. RESULTS: Sebaceous gland rich skin had an increased dermal lipid content compared to sebaceous gland poor skin to which all the tested sebum component lipids could contribute by penetrating through the dermo-epidermal barrier. Of the lipids, oleic and linoleic acids promoted monocyte differentiation into alternatively activated macrophages. Moreover, linoleic acid also had an anti-inflammatory effect in Propionibacterium acnes activated macrophages, inhibiting the secretion of IL-1B, IL-6 and TNF-Alpha. Squalene, palmitic, stearic and oleic acids augmented the secretion of IL-1B even in the absence of Propionibacterium acnes, while oleic acid had a selective effect of inducing IL-1B, but down-regulating IL-6 and TNF-A secretion. CONCLUSIONS: Our results suggest a role for sebaceous glands in modulating innate immune responses via their secreted lipids that are of possible pathologic and therapeutic relevance. This article is protected by copyright. All rights reserved

Leptin promotes a proinflammatory lipid profile and induces inflammatory pathways in human SZ95 sebocytes

Our findings suggest that leptin signalling may be involved in the proinflammatory regulation of sebaceous lipid metabolism and the induction of inflammatory enzymes and cytokines