Stat6 signaling suppresses VLA-4 expression by CD8+ T cells and limits their ability to infiltrate tumor lesions in vivo

Kotaro Sasaki, Xi Zhao, Angela D. Pardee, Ryo Ueda, Mitsugu Fujita, Sarita Sehra, Mark H. Kaplan, Lawrence P. Kane, Hideho Okada, Walter J. Storkus

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

VLA-4 plays a critical role in T cell trafficking into inflammatory sites. Our recent studies have suggested that VLA-4 expression on CD8 + T cells is negatively controlled by IL-4 and serves as a functionally distinguishing variable for why Type-1, but not Type-2, CD8 + T cells are able to traffic into tumors. In this study, using in vitro culture of murine CD8 + T cells under Type-1 and Type-2 cytokine conditions, we show that IL-4-mediated down-regulation of VLA-4 expression is completely abrogated in Stat6-deficient CD8 + T cells. Conversely, CD8 + T cells expressing a constitutively active mutant form Stat6 (Stat6VT) failed to express VLA-4 even in the absence of IL-4-stimuIation. Notably, Type-2 CD8 + T cells developed from Stat6 -/- but not wild-type mice were competent to migrate into tumor lesions in vivo. These results suggest that Stat6-signaling is necessary and sufficient to restrict CD8 + T cell expression of VLA-4 (by IL-4), thereby serving as a regulator for CD8 + T cell infiltration into tumors.

Original languageEnglish (US)
Pages (from-to)104-108
Number of pages5
JournalJournal of Immunology
Volume181
Issue number1
DOIs
StatePublished - Jan 1 2008

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Integrin alpha4beta1
T-Lymphocytes
Interleukin-4
Neoplasms
Down-Regulation
Cytokines

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Stat6 signaling suppresses VLA-4 expression by CD8+ T cells and limits their ability to infiltrate tumor lesions in vivo. / Sasaki, Kotaro; Zhao, Xi; Pardee, Angela D.; Ueda, Ryo; Fujita, Mitsugu; Sehra, Sarita; Kaplan, Mark H.; Kane, Lawrence P.; Okada, Hideho; Storkus, Walter J.

In: Journal of Immunology, Vol. 181, No. 1, 01.01.2008, p. 104-108.

Research output: Contribution to journalArticle

Sasaki, K, Zhao, X, Pardee, AD, Ueda, R, Fujita, M, Sehra, S, Kaplan, MH, Kane, LP, Okada, H & Storkus, WJ 2008, 'Stat6 signaling suppresses VLA-4 expression by CD8+ T cells and limits their ability to infiltrate tumor lesions in vivo', Journal of Immunology, vol. 181, no. 1, pp. 104-108. https://doi.org/10.4049/jimmunol.181.1.104
Sasaki, Kotaro ; Zhao, Xi ; Pardee, Angela D. ; Ueda, Ryo ; Fujita, Mitsugu ; Sehra, Sarita ; Kaplan, Mark H. ; Kane, Lawrence P. ; Okada, Hideho ; Storkus, Walter J. / Stat6 signaling suppresses VLA-4 expression by CD8+ T cells and limits their ability to infiltrate tumor lesions in vivo. In: Journal of Immunology. 2008 ; Vol. 181, No. 1. pp. 104-108.
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