Minireview: Nuclear Receptors, Hematopoiesis, and Stem Cells

Chute, John P.; Ross, Joel; McDonnell, Donald P.

doi:10.1210/me.2009-0332

Cited by 33 publications

(29 citation statements)

References 96 publications

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“…Similarly, systemic treatment of mice with the pan RAR inverse agonist BMS493 reduced pre-μDC, whereas intraperitoneal administration of all trans-RA or the RARα agonist AM580 increased the frequency and number of pre-μDCs dramatically. RA regulates hematopoietic progenitor development, and modulation of RARa/RXR signaling regulates hematopoietic stem cell (HSC) differentiation, proliferation, and self-renewal 19–21 . Furthermore, RA modulates neutrophil differentiation from myeloid progenitors under steady state conditions 22 .…”

Section: Discussionmentioning

confidence: 99%

Retinoic acid regulates the development of a gut-homing precursor for intestinal dendritic cells

et al. 2013

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The vitamin A metabolite retinoic acid (RA) regulates intestinal immune responses through immunomodulatory actions on intestinal dendritic cells (DCs) and lymphocytes. Here, we show that retinoic acid also controls the generation of gut-tropic migratory DC precursors, referred to as pre-mucosal DCs (pre-μDCs). Pre-μDCs express the gut trafficking receptor α4β7 and home preferentially to the intestines. They develop in the bone marrow, can differentiate into CCR9+ plasmacytoid DCs as well as conventional DCs (cDCs), but preferentially give rise to CD103+ intestinal cDCs. Generation of pre-μDCs in vivo in the bone marrow or in vitro is regulated by RA and retinoic acid receptor α signaling. The frequency of pre-μDCs is reduced in vitamin A-deficient animals and in animals treated with retinoic acid receptor inhibitors. The results define a novel vitamin A-dependent, retinoic-acid-regulated developmental sequence for dendritic cells and identify a targeted precursor for CD103+ cDCs in the gut.

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Section: Discussionmentioning

confidence: 99%

Retinoic acid regulates the development of a gut-homing precursor for intestinal dendritic cells

et al. 2013

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“…NR4A2, also known as Nurr1, is an orphan nuclear receptor [19]–[22], and its function in dopaminergic neuron signalling has been widely known. Increasing evidence suggests the role of NR4A2 in inflammatory responses during arthritis and psoriasis [23], [24], and NR4A2 may also serve as a regulatory element for reducing immune-mediated tissue damage [25].…”

Section: Introductionmentioning

confidence: 99%

Nuclear Receptor NR4A2 Orchestrates Th17 Cell-Mediated Autoimmune Inflammation via IL-21 Signalling

2013

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IL-17-producing CD4+ T helper 17 (Th17) cells are pathogenic in a range of human autoimmune diseases and corresponding animal models. We now demonstrate that such T cells infiltrating the target organ during the induction of experimental autoimmune encephalomyelitis (EAE) and experimental autoimmune uveoretinitis (EAU) specifically express NR4A2. Further, we reveal a critical involvement of NR4A2 in Th17 cell functions and Th17 cell-driven autoimmune diseases. When NR4A2 expression was blocked with siRNA, full Th17 differentiation was prevented in vitro: although cells expressed the master Th17 regulator, RORγt, they expressed reduced levels of IL-23R and were unable to produce IL-17 and IL-21. Notably, Th17 differentiation in the absence of NR4A2 was restored by exogenous IL-21, indicating that NR4A2 controls full maturation of Th17 cells via autocrine IL-21 signalling. Preventing NR4A2 expression in vivo by systemic treatment with NR4A2-specific siRNA also reduced Th17 effector responses and furthermore protected mice from EAE induction. In addition, the lack of disease was associated with a reduction in autocrine IL-21 production and IL-23R expression. Similar modulation of NR4A2 expression was also effective as an intervention, reversing established autoimmune responses and ameliorating clinical disease symptoms. Thus, NR4A2 appears to control Th17 differentiation and so plays an essential role in the development of Th17-mediated autoimmune disease. As NR4A2 is also upregulated during human autoimmune disease, targeting NR4A2 may provide a new therapeutic approach in treating autoimmune disease.

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confidence: 99%

A high concentration of triiodothyronine attenuates the stimulatory effect on hemin-induced erythroid differentiation of human erythroleukemia K562 cells

et al. 2015

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Thyroid hormone stimulates erythropoiesis and clinical hypothyroidism is often complicated by reductions in red cell mass and total blood volume, and by normocytic normochromic anemia [1][2][3][4]. Clinically, bone marrow has been observed to show erythroid hyperplasia in patients with hyperthyroidism [5]. However, anemia is sometimes observed in patients with hyperthyroidism such as Graves' disease (GD). Some reports indicate that anemia associated with hyperthyroidism occurs in 10-22% of cases of non-treated hyperthyroidism, and that these cases recover well with treatment of A high concentration of triiodothyronine attenuates the stimulatory effect on hemin-induced erythroid differentiation of human erythroleukemia K562 cells Abstract. Although thyroid hormone is a known stimulator of erythropoietic differentiation, severe anemia is sometimes observed in patients with hyperthyroidism and this mechanism is not fully understood. The aim of this study was to investigate the effect of triiodothyronine (T3) on hemin-induced erythropoiesis. Human erythroleukemia K562 cells were used as an erythroid differentiation model. Cell differentiation was induced by hemin and the effect of pre-incubation with T3 (0.1 to 100 nM) was analyzed by measuring the benzidine-positive rate, hemoglobin content, CD71 expression (transferrin receptor), and mRNA expression for transcription factors related to erythropoiesis and thyroid hormone receptors (TRs). Hemin, a promoter of erythroid differentiation, increased the levels of mRNAs for TRα, TRβ, and retinoid X receptor α (RXRα), as well as those for nuclear factor-erythroid 2 (NFE2), GATA-binding protein 1 (GATA1) and GATA-binding protein 2 (GATA2). Lower concentrations of T3 had a stimulatory effect on hemin-induced hemoglobin production (1 and 10 nM), CD71 expression (0.1 nM), and α-globin mRNA expression (1 nM), while a higher concentration of T3 (100 nM) abrogated the stimulatory effect on these parameters. T3 at 100 nM did not affect cell viability and proliferation, suggesting that the abrogation of erythropoiesis enhancement was not due to toxicity. T3 at 100 nM also significantly inhibited expression of GATA2 and RXRα mRNA, compared to 1 nM T3. We conclude that a high concentration of T3 attenuates the classical stimulatory effect on erythropoiesis exerted by a low concentration of T3 in hemin-induced K562 cells.

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Minireview: Nuclear Receptors, Hematopoiesis, and Stem Cells

Cited by 33 publications

References 96 publications

Retinoic acid regulates the development of a gut-homing precursor for intestinal dendritic cells

Retinoic acid regulates the development of a gut-homing precursor for intestinal dendritic cells

Nuclear Receptor NR4A2 Orchestrates Th17 Cell-Mediated Autoimmune Inflammation via IL-21 Signalling

A high concentration of triiodothyronine attenuates the stimulatory effect on hemin-induced erythroid differentiation of human erythroleukemia K562 cells

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