Increased TSLP availability restores T- and B-cell compartments in adult IL-7-deficient mice

Stephane Chappaz, Lukas Flueck, Andrew G. Farr, Antonius G. Rolink, Daniela Finke

Research output: Contribution to journalArticleResearchpeer-review

48 Citations (Scopus)

Abstract

Interleukin 7 (IL-7) plays a crucial role in adult lymphopoiesis, while in fetal life its effect can be partially compensated by TSLP. Whether adult hematopoietic progenitor cells are unresponsive to TSLP or whether TSLP is less available in adult microenvironments is still a matter of debate. Here, we show that increased TSLP availability through transgene (Tg) expression fully restored lymphopoiesis in IL-7-deficient mice: it rescued B-cell development, increased thymic and splenic cellularities, and restored doublenegative (DN) thymocytes, αβ and γδ T-cell generation, and all peripheral lymphoid compartments. Analysis of bone marrow chimeras demonstrated that hematopoietic progenitor cells from adult wild-type mice efficiently differentiated toward B- and T-cell lineages in lethally irradiated IL-7 deficient mice provided TSLP Tg was expressed in these mice. In vitro, TSLP promoted the differentiation of uncommitted adult bone marrow progenitors toward B and T lineages and the further differentiation of DN1 and DN2 thymocytes. Altogether, our results show that adult hematopoietic cells are TSLP responsive and that TSLP can sustain long-term adult lymphopoiesis.

Original languageEnglish
Pages (from-to)3862-3870
Number of pages9
JournalBlood
Volume110
Issue number12
DOIs
Publication statusPublished - 1 Dec 2007
Externally publishedYes

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