TCR-independent CD30 signaling selectively induces IL-13 production via a TNF receptor-associated factor/p38 mitogen-activated protein kinase-dependent mechanism

Helena Harlin, Eckhard Podack, Mark Boothby, Maria Luisa Alegre

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Initiation of T lymphocyte responses to most Ags requires concurrent stimulation through the TCR and costimulatory receptors such as CD28. Following initial activation, secondary receptors are up-regulated that can costimulate T cells in concert with TCR engagement. One such receptor is the TNFR family member CD30. In this study, we report that unlike CD28, ligation of CD30 on normal effector T cells induces IL-13 production in the absence of concurrent TCR engagement. TCR-independent CD30-mediated IL-13 release correlated with activation of c-Jun N-terminal kinase, p38 mitogen-activated protein kinase (MAPK), and NF-κB, and was completely inhibited by the expression of a TNFR-associated factor 2 (TRAF2) dominant-negative transgene (TRAF2.DN-Tg), but not by that of an I-κBα dominant-negative transgene. In parallel, expression of the TRAF2.DN-Tg selectively prevented the induction of c-Jun N-terminal kinase and p38 MAPK, but not that of NF-κB. Furthermore, IL-13 production was reduced in a dose-dependent manner by the p38 MAPK inhibitor SB203580. Together, these results suggest that TCR-independent CD30-mediated production of IL-13 is triggered by association of CD30 with TRAF family members and subsequent activation of p38 MAPK. Inasmuch as IL-13 can promote airway inflammation and cancer progression, production of IL-13 in a TCR-independent manner has important pathological implications in vivo.

Original languageEnglish
Pages (from-to)2451-2460
Number of pages10
JournalJournal of Immunology
Volume169
Issue number5
StatePublished - Sep 1 2002
Externally publishedYes

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Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
Interleukin-13
p38 Mitogen-Activated Protein Kinases
JNK Mitogen-Activated Protein Kinases
T-Lymphocytes
Transgenes
Proto-Oncogene Proteins c-akt
Protein Kinase Inhibitors
Ligation
Inflammation

ASJC Scopus subject areas

  • Immunology

Cite this

TCR-independent CD30 signaling selectively induces IL-13 production via a TNF receptor-associated factor/p38 mitogen-activated protein kinase-dependent mechanism. / Harlin, Helena; Podack, Eckhard; Boothby, Mark; Alegre, Maria Luisa.

In: Journal of Immunology, Vol. 169, No. 5, 01.09.2002, p. 2451-2460.

Research output: Contribution to journalArticle

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