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Blood, 1 December 2007, Vol. 110, No. 12, pp. 3862-3870.
Prepublished online as a Blood First Edition Paper on August 16, 2007; DOI 10.1182/blood-2007-02-074245.
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Submitted February 15, 2007
Accepted August 11, 2007
Increased TSLP availability restores T and B cell
compartments in adult IL-7 deficient mice
S. Chappaz, L. Flueck, A. G. Farr, A. G. Rolink, and D. Finke*
Department of Clinical and Biological Sciences, Center for Biomedicine, University of Basel, Basel, Switzerland
Department of Biological Structure, University of Washington, Seattle, WA, United States
* Corresponding author; email: daniela.finke{at}unibas.ch.
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, restored double negative (DN) thymocytes,  and  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 towards 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 towards 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.

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