Thyroid hormone T3 acting through the thyroid hormone alpha receptor is necessary for implementation of erythropoiesis in the neonatal spleen environment in the mouse.
Thyroid hormones (THs) mediate many physiological and developmental functions in vertebrates. All these functions are mediated by binding of the active form of the TH T3 to the specific nuclear receptors TRalpha and TRbeta, which are transcription factors. Using mutant mice lacking TRs or deficient for TH production, we show that T3 influences neonatal erythropoiesis through TRalpha. The effect of T3 and TRalpha is restricted to this developmental window and is specific for the spleen but not for other erythropoietic organs. We show that T3 via TRalpha affects late steps of erythrocytic development, promoting the proliferation of late basophilic erythroblasts. In vitro, this effect is exerted directly on erythrocytic cells. In vivo, the action of T3 is also intrinsic to spleen erythrocytic progenitors, as shown by grafting experiments of splenocytes derived from wildtype and TRalpha knockout (TRalpha(0/0)) mice into wild-type and TRalpha(0/0) irradiated recipients. Our results indicate that defective spleen erythropoiesis in hypothyroid and TRalpha(0/0) mice results from impaired recognition of the spleen environment by the mutant erythrocytic progenitors. The data presented support a model in which T3 signaling through TRalpha is essential for the implementation of the transient spleen erythropoiesis at birth.
Angelin-Duclos
Cristina
C
Ecole Normale Supérieure de Lyon, UMR CNRS 5161, INRA 1237, IFR128 Biosciences Lyon-Gerland, 46 Allée d'Italie, 69364 Lyon Cedex 07, France.
Domenget
Chantal
C
Kolbus
Andrea
A
Beug
Hartmut
H
Jurdic
Pierre
P
Samarut
Jacques
J
D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D004912:Erythrocytes / Q000378:metabolism; D004920:Erythropoiesis; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008954:Models, Biological; D010641:Phenotype; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D013234:Stem Cells; D037021:Thyroid Hormone Receptors alpha / Q000502:physiology*; D013997:Time Factors; D014284:Triiodothyronine / Q000502:physiology*
D037021:Thyroid Hormone Receptors alpha; D014284:Triiodothyronine