M Lovászi1, M Mattii2, K Eyerich3, A Gácsi4, E Csányi4, D Kovács1, R Rühl5, A Szegedi1,6, L Kemény7,8, M Ståhle9, C C Zouboulis10, S Eyerich2, D Törőcsik1,9. 1. Department of Dermatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary. 2. ZAUM - Centre for Allergy and Environment, Technische Universität and Helmholtz Centre Munich, Member of the German Centre for Lung Research (DZL), Munich, Germany. 3. Department of Dermatology and Allergy, Technische Universität Munich, Munich, Germany. 4. Institute of Pharmaceutical Technology and Regulatory Affairs, Faculty of Pharmacy, University of Szeged, Szeged, Hungary. 5. MTA-DE Public Health Research Group of the Hungarian Academy of Sciences, Faculty of Public Health, University of Debrecen, Debrecen, Hungary. 6. Division of Dermatological Allergology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary. 7. Department of Dermatology and Allergology, University of Szeged, Szeged, Hungary. 8. MTA-SZTE Dermatological Research Group, University of Szeged, Szeged, Hungary. 9. Unit of Dermatology and Venereology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. 10. Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Centre, Brandenburg Medical School Theodore Fontane, Dessau, Germany.
Abstract
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. OBJECTIVES: 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 fluorescein isothiocyanate-conjugated P. acnes were detected by fluorescence-activated cell sorting measurements. Cytokine protein levels were evaluated by enzyme-linked immunosorbent assay and Western blot analysis. RESULTS: Sebaceous gland-rich skin had an increased dermal lipid content vs. sebaceous gland-poor skin to which all the tested sebum component lipids could contribute by penetrating the dermoepidermal barrier. Of the lipids, oleic acid and linoleic acid promoted monocyte differentiation into alternatively activated macrophages. Moreover, linoleic acid also had an anti-inflammatory effect in P. acnes-activated macrophages, inhibiting the secretion of interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-α. Squalene, palmitic acid, stearic acid and oleic acid augmented the secretion of IL-1β, even in the absence of P. acnes, whereas oleic acid had a selective effect of inducing IL-1β but downregulating IL-6 and TNF-α secretion. CONCLUSIONS: Our results suggest a role for sebaceous glands in modulating innate immune responses via their secreted lipids that are of possible pathological and therapeutic relevance.
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. OBJECTIVES: 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 fluorescein isothiocyanate-conjugated P. acnes were detected by fluorescence-activated cell sorting measurements. Cytokine protein levels were evaluated by enzyme-linked immunosorbent assay and Western blot analysis. RESULTS: Sebaceous gland-rich skin had an increased dermal lipid content vs. sebaceous gland-poor skin to which all the tested sebum component lipids could contribute by penetrating the dermoepidermal barrier. Of the lipids, oleic acid and linoleic acid promoted monocyte differentiation into alternatively activated macrophages. Moreover, linoleic acid also had an anti-inflammatory effect in P. acnes-activated macrophages, inhibiting the secretion of interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-α. Squalene, palmitic acid, stearic acid and oleic acid augmented the secretion of IL-1β, even in the absence of P. acnes, whereas oleic acid had a selective effect of inducing IL-1β but downregulating IL-6 and TNF-α secretion. CONCLUSIONS: Our results suggest a role for sebaceous glands in modulating innate immune responses via their secreted lipids that are of possible pathological and therapeutic relevance.
Authors: Tran H Do; Feiyang Ma; Priscila R Andrade; Rosane Teles; Bruno J de Andrade Silva; Chanyue Hu; Alejandro Espinoza; Jer-En Hsu; Chun-Seok Cho; Myungjin Kim; Jingyue Xi; Xianying Xing; Olesya Plazyo; Lam C Tsoi; Carol Cheng; Jenny Kim; Bryan D Bryson; Alan M O'Neill; Marco Colonna; Johann E Gudjonsson; Eynav Klechevsky; Jun Hee Lee; Richard L Gallo; Barry R Bloom; Matteo Pellegrini; Robert L Modlin Journal: Sci Immunol Date: 2022-07-22
Authors: Gabriella Béke; Zsolt Dajnoki; Anikó Kapitány; Krisztián Gáspár; Barbara Medgyesi; Szilárd Póliska; Zoltán Hendrik; Zoltán Péter; Dániel Törőcsik; Tamás Bíró; Andrea Szegedi Journal: Front Immunol Date: 2018-03-05 Impact factor: 7.561