Ceramide synthase 2 null mice are protected from ovalbumin-induced asthma with higher t cell receptor signal strength in cd4+ t cells

Sun Hye Shin, Kyung Ah Cho, Hee Soo Yoon, So Yeon Kim, Hee Yeon Kim, Yael Pewzner-Jung, Sung Ae Jung, Woo Jae Park, Anthony H. Futerman, Joo Won Park

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number2713
Pages (from-to)1-18
Number of pages18
JournalInternational Journal of Molecular Sciences
Volume22
Issue number5
DOIs
StatePublished - 1 Mar 2021

Keywords

  • Asthma
  • Ceramide
  • Ceramide synthase 2
  • Chain length
  • T cell receptor strength

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