Increased TSLP availability restores T- and B-cell compartments in adult IL-7 deficient mice.
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 double-negative (DN) thymocytes, alphabeta and gammadelta 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.
Chappaz
Stephane
S
Center for Biomedicine, Department of Clinical and Biological Sciences (DKBW), University of Basel, Basel, Switzerland.
Flueck
Lukas
L
Farr
Andrew G
AG
Rolink
Antonius G
AG
Finke
Daniela
D
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation / Q000235:genetics; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D015851:Interleukin-7 / Q000235:genetics / Q000378:metabolism; D054503:Lymphoid Progenitor Cells / Q000166:cytology / Q000378:metabolism*; D038041:Lymphopoiesis / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D013950:Thymus Gland / Q000378:metabolism; D019076:Transgenes / Q000502:physiology; D018183:Transplantation Chimera; D000094632:Thymic Stromal Lymphopoietin
D016207:Cytokines; D015851:Interleukin-7; D016693:Receptors, Antigen, T-Cell, alpha-beta; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse