Glucocorticoids inhibit human hematopoietic stem cell differentiation toward a common ILC precursor

Quatrini, Linda; Tumino, Nicola; Besi, Francesca; Ciancaglini, Cecilia; Galaverna, Federica; Grasso, A.; Merli, Pietro; Locatelli, Franco; Vacca, Paola; Moretta, Lorenzo

doi:10.1016/j.jaci.2021.10.012

Cited by 6 publications

(4 citation statements)

References 58 publications

(75 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…206 In line with this finding is GC-induced upregulation of PRDM1, which encodes BLIMP-1, a gene that promotes differentiation of B cells to plasma cells. 206 GCs also favor the generation of NK cells from myeloid precursors, 221 whereas their proliferation, as well as their ability to lyse tubular endothelial cells, was significantly inhibited by prednisolone. 96…”

Section: Corticosteroidsmentioning

confidence: 99%

Cellular Immunobiology and Molecular Mechanisms in Alloimmunity—Pathways of Immunosuppression

et al. 2023

View full text Add to dashboard Cite

Current maintenance immunosuppression commonly comprises a synergistic combination of tacrolimus as calcineurin inhibitor (CNI), mycophenolic acid, and glucocorticoids. Therapy is often individualized by steroid withdrawal or addition of belatacept or inhibitors of the mechanistic target of rapamycin. This review provides a comprehensive overview of their mode of action, focusing on the cellular immune system. The main pharmacological action of CNIs is suppression of the interleukin-2 pathway that leads to inhibition of T cell activation. Mycophenolic acid inhibits the purine pathway and subsequently diminishes T and B cell proliferation but also exerts a variety of effects on almost all immune cells, including inhibition of plasma cell activity. Glucocorticoids exert complex regulation via genomic and nongenomic mechanisms, acting mainly by downregulating proinflammatory cytokine signatures and cell signaling. Belatacept is potent in inhibiting B/T cell interaction, preventing formation of antibodies; however, it lacks the potency of CNIs in preventing T cell-mediated rejections. Mechanistic target of rapamycin inhibitors have strong antiproliferative activity on all cell types interfering with multiple metabolic pathways, partly explaining poor tolerability, whereas their superior effector T cell function might explain their benefits in the case of viral infections. Over the past decades, clinical and experimental studies provided a good overview on the underlying mechanisms of immunosuppressants. However, more data are needed to delineate the interaction between innate and adaptive immunity to better achieve tolerance and control of rejection. A better and more comprehensive understanding of the mechanistic reasons for failure of immunosuppressants, including individual risk/benefit assessments, may permit improved patient stratification.

show abstract

Section: Corticosteroidsmentioning

confidence: 99%

Cellular Immunobiology and Molecular Mechanisms in Alloimmunity—Pathways of Immunosuppression

et al. 2023

View full text Add to dashboard Cite

show abstract

“…In addition to impacting bone biology, BMAds and GC have independent effects on hematopoiesis (39)(40)(41)(42). To determine if loss of GR in BMAds impacts hematopoiesis, we measured complete blood counts from male and female BMAd-Nr3c1 +/+ and BMAd- Nr3c1 -/mice.…”

Section: Deletion Of Nr3c1 In Bmads Alters Circulating White Blood Ce...mentioning

confidence: 99%

Deficiency of glucocorticoid receptor in bone marrow adipocytes has mild effects on bone and hematopoiesis but does not influence expansion of marrow adiposity with caloric restriction

Schill,

Visser,

Ashby

et al. 2024

Front. Endocrinol.

View full text Add to dashboard Cite

IntroductionUnlike white adipose tissue depots, bone marrow adipose tissue (BMAT) expands during caloric restriction (CR). Although mechanisms for BMAT expansion remain unclear, prior research suggested an intermediary role for increased circulating glucocorticoids. MethodsIn this study, we utilized a recently described mouse model (BMAd-Cre) to exclusively target bone marrow adipocytes (BMAds) for elimination of the glucocorticoid receptor (GR) (i.e. Nr3c1) whilst maintaining GR expression in other adipose depots. ResultsMice lacking GR in BMAds (BMAd-Nr3c1-/-) and control mice (BMAd-Nr3c1+/+) were fed ad libitum or placed on a 30% CR diet for six weeks. On a normal chow diet, tibiae of female BMAd-Nr3c1-/- mice had slightly elevated proximal trabecular metaphyseal bone volume fraction and thickness. Both control and BMAd-Nr3c1-/- mice had increased circulating glucocorticoids and elevated numbers of BMAds in the proximal tibia following CR. However, no significant differences in trabecular and cortical bone were observed, and quantification with osmium tetroxide and μCT revealed no difference in BMAT accumulation between control or BMAd-Nr3c1-/- mice. Differences in BMAd size were not observed between BMAd-Nr3c1-/- and control mice. Interestingly, BMAd-Nr3c1-/- mice had decreased circulating white blood cell counts 4 h into the light cycle.DiscussionIn conclusion, our data suggest that eliminating GR from BMAd has minor effects on bone and hematopoiesis, and does not impair BMAT accumulation during CR.

show abstract

“…In our example panel (Figure 2), we used CD3, CD19, and CD14 to exclude T cells, B cells and monocytes, respectively [16]. To make a more accurate exclusion of non‐ILCs, it is recommended to also include in the lineage CD34, TCRαβ, TCRγδ, CD123, CD15, and FcεRI.…”

Section: Human Pb Ilc Gating Strategymentioning

confidence: 99%

CPHEN‐15: Comprehensive phenotyping of human peripheral blood helper‐ILCs by flow cytometry

et al. 2023

Self Cite

View full text Add to dashboard Cite

Innate lymphoid cells (ILCs) comprise cytotoxic NK cells and helper-ILCs, which are further divided in ILC1, ILC2, and ILC3. Helper-ILCs mirror the effector functions of helper T-cell subsets and contribute to host immune defense, tissue homeostasis and repair through cytokine secretion. Although they are mainly tissue-resident, helper ILCs are also found in the peripheral blood (PB). In the human setting, it may be needed to analyze circulating helper ILCs to compare pathological to physiological conditions. In this review, we provide simple guidelines and a list of markers useful to study human PB helper ILCs phenotype and function by flow cytometry.

show abstract

Glucocorticoids inhibit human hematopoietic stem cell differentiation toward a common ILC precursor

Cited by 6 publications

References 58 publications

Cellular Immunobiology and Molecular Mechanisms in Alloimmunity—Pathways of Immunosuppression

Cellular Immunobiology and Molecular Mechanisms in Alloimmunity—Pathways of Immunosuppression

Deficiency of glucocorticoid receptor in bone marrow adipocytes has mild effects on bone and hematopoiesis but does not influence expansion of marrow adiposity with caloric restriction

CPHEN‐15: Comprehensive phenotyping of human peripheral blood helper‐ILCs by flow cytometry

Contact Info

Product

Resources

About