CD30 ligand/CD30 plays a critical role in Th17 differentiation in mice

Xun Sun, Hisakata Yamada, Kensuke Shibata, Hiromi Muta, Kenzaburo Tani, Eckhard R. Podack, Yasunobu Yoshikai

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35 Scopus citations

Abstract

A CD30 ligand (CD30L; CD153) and its receptor, CD30, is a membrane-associated glycoprotein belonging to the TNF superfamily and TNFR superfamily. These were expressed preferentially by activated CD4+T cells. In this paper, we show that CD44lowCD62hi CD4 + T cells from CD30L-/- or CD30-/- mice exhibited impaired differentiation into Th17 cells but an increased ability to produce IL-2 after in vitro culture under Th17-polarizing conditions. Neutralization with IL-2 by anti-IL-2 mAb partly restored the ability of Th17 differentiation in CD30L-/- or CD30-/- T cells. Stimulation via CD30L by immobilized anti-CD30L mAb suppressed IL-2 production by CD30-/-CD4+ T cells, indicating that the reverse signal to CD30L is responsible for down-regulation of IL-2 production. In vivo Th17 differentiation of CD30L-/-CD4+CD45RBhigh T cells was also impaired after transfer into SCID mice, whereas CD30L +/+CD4+CD45RBhigh T cells normally differentiated into Th17 cells in CD30L-/-SCID mice. The results of these studies demonstrate that CD30L/CD30 signaling executed by the T-T cell interaction plays a critical role in Th17 cell differentiation, at least partly via downregulation of IL-2 production.

Original languageEnglish
Pages (from-to)2222-2230
Number of pages9
JournalJournal of Immunology
Volume185
Issue number4
DOIs
StatePublished - Aug 15 2010
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Sun, X., Yamada, H., Shibata, K., Muta, H., Tani, K., Podack, E. R., & Yoshikai, Y. (2010). CD30 ligand/CD30 plays a critical role in Th17 differentiation in mice. Journal of Immunology, 185(4), 2222-2230. https://doi.org/10.4049/jimmunol.1000024