Sun-Hye Shin1, Kyung-Ah Cho2, Hee-Soo Yoon1, So-Yeon Kim1, Hee-Yeon Kim1, Yael Pewzner-Jung3, Sung-Ae Jung4, Woo-Jae Park5, Anthony H Futerman3, Joo-Won Park1. 1. Department of Biochemistry, College of Medicine, Ewha Womans University, Seoul 07804, Korea. 2. Department of Microbiology, College of Medicine, Ewha Womans University, Seoul 07804, Korea. 3. Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 76100, Israel. 4. Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul 07804, Korea. 5. Department of Biochemistry, College of Medicine, Gachon University, Incheon 21999, Korea.
Abstract
(1) Background: six mammalian ceramide synthases (CerS1-6) determine the acyl chain length of sphingolipids (SLs). Although ceramide levels are increased in murine allergic asthma models and in asthmatic patients, the precise role of SLs with specific chain lengths is still unclear. The role of CerS2, which mainly synthesizes C22-C24 ceramides, was investigated in immune responses elicited by airway inflammation using CerS2 null mice. (2) Methods: asthma was induced in wild type (WT) and CerS2 null mice with ovalbumin (OVA), and inflammatory cytokines and CD4 (cluster of differentiation 4)+ T helper (Th) cell profiles were analyzed. We also compared the functional capacity of CD4+ T cells isolated from WT and CerS2 null mice. (3) Results: CerS2 null mice exhibited milder symptoms and lower Th2 responses than WT mice after OVA exposure. CerS2 null CD4+ T cells showed impaired Th2 and increased Th17 responses with concomitant higher T cell receptor (TCR) signal strength after TCR stimulation. Notably, increased Th17 responses of CerS2 null CD4+ T cells appeared only in TCR-mediated, but not in TCR-independent, treatment. (4) Conclusions: altered Th2/Th17 immune response with higher TCR signal strength was observed in CerS2 null CD4+ T cells upon TCR stimulation. CerS2 and very-long chain SLs may be therapeutic targets for Th2-related diseases such as asthma.
(1) Background: six mammalianceramide synthases (CerS1-6) determine the acyl chain length of sphingolipids (SLs). Although ceramide levels are increased in murineallergic asthma models and in asthmatic patients, the precise role of SLs with specific chain lengths is still unclear. The role of CerS2, which mainly synthesizes C22-C24 ceramides, was investigated in immune responses elicited by airway inflammation using CerS2 null mice. (2) Methods:asthma was induced in wild type (WT) and CerS2 null mice with ovalbumin (OVA), and inflammatory cytokines and CD4 (cluster of differentiation 4)+ T helper (Th) cell profiles were analyzed. We also compared the functional capacity of CD4+ T cells isolated from WT and CerS2 null mice. (3) Results:CerS2 null mice exhibited milder symptoms and lower Th2 responses than WT mice after OVA exposure. CerS2 null CD4+ T cells showed impaired Th2 and increased Th17 responses with concomitant higher T cell receptor (TCR) signal strength after TCR stimulation. Notably, increased Th17 responses of CerS2 null CD4+ T cells appeared only in TCR-mediated, but not in TCR-independent, treatment. (4) Conclusions: altered Th2/Th17 immune response with higher TCR signal strength was observed in CerS2 null CD4+ T cells upon TCR stimulation. CerS2 and very-long chain SLs may be therapeutic targets for Th2-related diseases such as asthma.
Authors: Briana N James; Clement Oyeniran; Jamie L Sturgill; Jason Newton; Rebecca K Martin; Erhard Bieberich; Cynthia Weigel; Melissa A Maczis; Elisa N D Palladino; Joseph C Lownik; John B Trudeau; Joan M Cook-Mills; Sally Wenzel; Sheldon Milstien; Sarah Spiegel Journal: J Allergy Clin Immunol Date: 2020-10-29 Impact factor: 14.290
Authors: Stephen T Holgate; Sally Wenzel; Dirkje S Postma; Scott T Weiss; Harald Renz; Peter D Sly Journal: Nat Rev Dis Primers Date: 2015-09-10 Impact factor: 52.329