Development of regulatory T cells requires IL-7Rα stimulation by IL-7 or TSLP
| Autor: | Arthur A. Hurwitz, Renata Mazzucchelli, Scott K. Durum, Jami Willette-Brown, Julie A. Hixon, Wenqing Li, Warren J. Leonard, Veronica L. Hall, Rosanne Spolski, Xin Chen |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Male
Stromal cell Thymic stromal lymphopoietin medicine.medical_treatment Immunology Mice Transgenic chemical and pharmacologic phenomena Cell Separation Thymus Gland Biology T-Lymphocytes Regulatory Biochemistry Mice Immune system Thymic Stromal Lymphopoietin medicine Animals Cytotoxic T cell IL-2 receptor Immunobiology Receptors Interleukin-7 Interleukin-7 Cell Membrane FOXP3 hemic and immune systems Cell Biology Hematology Cell biology Mice Inbred C57BL Phenotype Cytokine Cytokines Female Tumor necrosis factor alpha Gene Deletion |
| Zdroj: | Blood. 112:3283-3292 |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | Interleukin-7 (IL-7), a cytokine produced by stromal cells, is required for thymic development and peripheral homeostasis of most major subsets of T cells. We examined whether regulatory T (Treg) cells also required the IL-7 pathway by analyzing IL-7Rα−/− mice. We observed a striking reduction in cells with the Treg surface phenotype (CD4, CD25, GITR (glucocorticoid-induced tumor necrosis factor [TNF]-like receptor), CD45RB, CD62L, CD103) or intracellular markers (cytotoxic T-lymphocyte–associated antigen-4, CTLA-4, and forkhead box transcription factor 3, Foxp3). Foxp3 transcripts were virtually absent in IL-7Rα−/− lymphoid tissues, and no Treg cell suppressive activity could be detected. There are 2 known ligands for IL-7Rα: IL-7 itself and thymic stromal lymphopoietin (TSLP). Surprisingly, mice deficient in IL-7 or the other chain of the TSLP receptor (TSLPR) developed relatively normal numbers of Treg cells. Combined deletion of IL-7 and TSLP receptor greatly reduced Treg cell development in the thymus but was not required for survival of mature peripheral Treg cells. We conclude that Treg cells, like other T cells, require signals from the IL-7 receptor, but unlike other T cells, do not require IL-7 itself because of at least partially overlapping actions of IL-7 and TSLP for development of Treg cells. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|