Stat6 Signaling Suppresses VLA-4 Expression by CD8+ T Cells and Limits Their Ability to Infiltrate Tumor Lesions In Vivo
| العنوان: | Stat6 Signaling Suppresses VLA-4 Expression by CD8+ T Cells and Limits Their Ability to Infiltrate Tumor Lesions In Vivo |
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| المؤلفون: | Walter J. Storkus, Mitsugu Fujita, Sarita Sehra, Ryo Ueda, Lawrence P. Kane, Hideho Okada, Xi Zhao, Mark H. Kaplan, Angela D. Pardee, Kotaro Sasaki |
| المصدر: | Scopus-Elsevier |
| بيانات النشر: | The American Association of Immunologists, 2008. |
| سنة النشر: | 2008 |
| مصطلحات موضوعية: | ZAP70, T cell, Immunology, respiratory system, Biology, Natural killer T cell, CCL5, Cell biology, Interleukin 21, medicine.anatomical_structure, medicine, Immunology and Allergy, Cytotoxic T cell, IL-2 receptor, Antigen-presenting cell |
| الوصف: | 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-stimulation. 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. |
| تدمد: | 1550-6606 0022-1767 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::46faf61f4a91842a3e04694bcb74ec7eTest https://doi.org/10.4049/jimmunol.181.1.104Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....46faf61f4a91842a3e04694bcb74ec7e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15506606 00221767 |
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