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Development of regulatory T cells requires IL-7R{alpha} stimulation by IL-7 or TSLP
Mazzucchelli R.1; Hixon J.A.1; Spolski R.2; Chen X.3; Li W.Q.1; Hall V.L.1; Willette-Brown J.1; Hurwitz A.A.1; Leonard W.J.2; Durum S.K.1
2008-10-15
Source PublicationBlood
ISSN00064971 15280020
Volume112Issue:8Pages:3283-3292
Abstract

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-lymphoeyteassociated 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. Copyright 2007 by The American Society of Hematology; all rights reserved.

DOI10.1182/blood-2008-02-137414
URLView the original
Indexed BySCI
WOS Research AreaHematology
WOS SubjectHematology
WOS IDWOS:000259866100044
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Cited Times [WOS]:85   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.National Cancer Institute at Frederick
2.National Heart, Lung, and Blood Institute
3.SAIC-Frederick
Recommended Citation
GB/T 7714
Mazzucchelli R.,Hixon J.A.,Spolski R.,et al. Development of regulatory T cells requires IL-7R{alpha} stimulation by IL-7 or TSLP[J]. Blood,2008,112(8):3283-3292.
APA Mazzucchelli R..,Hixon J.A..,Spolski R..,Chen X..,Li W.Q..,...&Durum S.K..(2008).Development of regulatory T cells requires IL-7R{alpha} stimulation by IL-7 or TSLP.Blood,112(8),3283-3292.
MLA Mazzucchelli R.,et al."Development of regulatory T cells requires IL-7R{alpha} stimulation by IL-7 or TSLP".Blood 112.8(2008):3283-3292.
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