Development of regulatory T cells requires IL-7Rα stimulation by IL-7 or TSLP

• Published in: Blood Vol. 112; no. 8; pp. 3283 - 3292
• Main Authors: Mazzucchelli, Renata, Hixon, Julie A., Spolski, Rosanne, Chen, Xin, Li, Wen Qing, Hall, Veronica L., Willette-Brown, Jami, Hurwitz, Arthur A., Leonard, Warren J., Durum, Scott K.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15.10.2008; American Society of Hematology
• Series: Immunobiology
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2008-02-137414

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.