Deciphering the Complexities of Adult Human Steady State and Stress-Induced Hematopoiesis: Progress and Challenges DOI Open Access
Suzanne M. Watt, Maria G. Roubelakis

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 671 - 671

Published: Jan. 14, 2025

Human hematopoietic stem cells (HSCs) have traditionally been viewed as self-renewing, multipotent with enormous potential in sustaining essential steady state blood and immune cell production throughout life. Indeed, around 86% (1011-1012) of new generated daily a healthy young human adult are origin. Therapeutically, HSCs contributed to over 1.5 million transplants (HCTs) globally, making this the most successful regenerative therapy date. We will commence review by briefly highlighting selected key achievements (from 1868 end 20th century) that accomplishment. Much our knowledge hematopoiesis is based on small animal models that, despite their importance, do not always recapitulate hematopoiesis. Given this, we critically progress challenges faced identifying tracing lineage differentiation trajectories, referring murine studies needed. Moving forward given dynamic can readily adjust variety stressors, then discuss recent research advances contributing understanding (i) which HSPCs maintain hematopoiesis, (ii) where these located, (iii) mechanisms come into play when homeostatic switches stress-induced or emergency

Language: Английский

From virtual patients to digital twins in immuno-oncology: lessons learned from mechanistic quantitative systems pharmacology modeling DOI Creative Commons
Hanwen Wang, Theinmozhi Arulraj,

Alberto Ippolito

et al.

npj Digital Medicine, Journal Year: 2024, Volume and Issue: 7(1)

Published: July 16, 2024

Virtual patients and digital patients/twins are two similar concepts gaining increasing attention in health care with goals to accelerate drug development improve patients' survival, but their own limitations. Although methods have been proposed generate virtual patient populations using mechanistic models, there limited number of applications immuno-oncology research. Furthermore, due the stricter requirements twins, they often generated a study-specific manner models customized particular clinical settings (e.g., treatment, cancer, data types). Here, we discuss challenges for generation our most recent experiences, initiatives develop how research on these can inform each other.

Language: Английский

Citations

9
Role of gut microbiota and immune cells in metabolic-associated fatty liver disease: clinical impact DOI
Anna Alisi, Geoffrey W. McCaughan, Henning Grønbæk

et al.

Hepatology International, Journal Year: 2024, Volume and Issue: 18(S2), P. 861 - 872

Published: July 12, 2024

Language: Английский

Citations

8
Immune dynamics throughout life in relation to sex hormones and perspectives gained from gender-affirming hormone therapy DOI Creative Commons
Ahmet Yalçınkaya, Rümeysa Yalçınkaya,

Fabian Sardh

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 16, 2025

Biological sex is closely associated with the properties and extent of immune response, males females showing different susceptibilities to diseases variations in immunity. Androgens, predominantly males, generally suppress responses, while estrogens, more abundant females, tend enhance It also established that hormones at least partially explain biases diseases, particularly autoimmune females. These differences are influenced by hormonal, genetic, environmental factors, vary throughout life stages. The advent gender-affirming hormone therapy offers a novel opportunity study immunological effects hormones. Despite limited studies on this topic, available research has revealed testosterone transgender men may certain functions, such as type I interferon increasing inflammation markers like TNF-α. Transgender women estrogen experience alterations coagulation-related inflammatory characteristics. Furthermore, other possible regulation can be inferred from assessment individuals receiving therapy. Understanding complex interactions between system, through unique perspective offered therapies, facilitate development targeted therapies for infections improving healthcare outcomes individuals. Here we review dynamics both sexes provide summary findings drawn exploring

Language: Английский

Citations

1
Single cell suppression profiling of human regulatory T cells DOI Creative Commons
Jonas Nørskov Søndergaard, Janyerkye Tulyeu, David G. Priest

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 3, 2025

Regulatory T cells (Treg) play an important role in regulating immune homeostasis health and disease. Traditionally their suppressive function has been assayed by mixing purified cell populations, which does not provide accurate picture of a physiologically relevant response. To overcome this limitation, we here develop 'single suppression profiling human Tregs' (scSPOT). scSPOT uses 52-marker CyTOF panel, division detection algorithm, whole PBMC system to assess the effect Tregs on all other types simultaneously. In head-to-head comparison, find having clearest effects effector memory CD8 through partial arrest, cycle inhibition, molecule downregulation. Additionally, identifies Treg phenotypic split previously observed viral infection propose modes action FDA-approved drugs Ipilimumab Tazemetostat. is thus scalable, robust, widely applicable, may be used better understand immunobiology screen for therapeutic compounds. Traditional regulatory (Tregs) assays utilize mixture population. Here authors (scSPOT) with

Language: Английский

Citations

1
Defining immune reset: achieving sustained remission in autoimmune diseases DOI
Tobias Junt, Thomas Calzascia,

Elisabetta Traggiai

et al.

Nature reviews. Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: March 5, 2025

Language: Английский

Citations

1
Inflammation and aging-related disease: A transdisciplinary inflammaging framework DOI
Brian J. Andonian, Joseph A. Hippensteel, Katrina Abuabara

et al.

GeroScience, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Language: Английский

Citations

8
Mechanical control of antigen detection and discrimination by T and B cell receptors DOI Creative Commons
Jhordan Rogers, Anna T. Bajur, Khalid Salaita

et al.

Biophysical Journal, Journal Year: 2024, Volume and Issue: 123(15), P. 2234 - 2255

Published: May 23, 2024

The adaptive immune response is orchestrated by just two cell types, T cells and B cells. Both possess the remarkable ability to recognize virtually any antigen through their respective receptors-the receptor (TCR) (BCR). Despite extensive investigations into biochemical signaling events triggered recognition in these cells, our predict or control outcome of activation remains elusive. This challenge compounded sensitivity biophysical properties antigens presenting them-a phenomenon we are beginning understand. Recent insights underscore central role mechanical forces this process, governing conformation, activity, spatial organization TCRs BCRs within membrane, ultimately eliciting distinct cellular responses. Traditionally, have been studied independently, with researchers working parallel decipher mechanisms activation. While unveiled many overlaps how types sense respond antigens, notable differences exist. To fully grasp biology harness it for therapeutic purposes, distinctions must be considered. review compares contrasts TCR BCR, placing emphasis on force regulating activity both receptors shape humoral

Language: Английский

Citations

7
Advances and applications in single-cell and spatial genomics DOI
Jingjing Wang, Fang Ye, Haoxi Chai

et al.

Science China Life Sciences, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 20, 2024

Language: Английский

Citations

7
Small-molecule CBP/p300 histone acetyltransferase inhibition mobilizes leukocytes from the bone marrow via the endocrine stress response DOI Creative Commons

Nikolai Jaschke,

Dorit Breining,

Maura Hofmann

et al.

Immunity, Journal Year: 2024, Volume and Issue: 57(2), P. 364 - 378.e9

Published: Jan. 31, 2024

Mutations of the CBP/p300 histone acetyltransferase (HAT) domain can be linked to leukemic transformation in humans, suggestive a checkpoint leukocyte compartment sizes. Here, we examined impact reversible inhibition this by small-molecule A485. We found that A485 triggered acute and transient mobilization leukocytes from bone marrow into blood. Leukocyte was equally potent as, but mechanistically distinct from, granulocyte colony-stimulating factor (G-CSF), which allowed for additive neutrophil when both compounds were combined. These effects maintained models leukopenia conferred augmented host defenses. Mechanistically, activation hypothalamus-pituitary-adrenal gland (HPA) axis relayed shifts distribution through corticotropin-releasing hormone receptor 1 (CRHR1) adrenocorticotropic (ACTH), independently glucocorticoids. Our findings identify strategy rapid expansion blood via neuroendocrine loop, with implications treatment human pathologies.

Language: Английский

Citations

6
LymphoDose: a lymphocyte dose estimation framework—application to brain radiotherapy DOI Creative Commons
François de Kermenguy, Nathan Benzazon, Pauline Maury

et al.

Physics in Medicine and Biology, Journal Year: 2024, Volume and Issue: 69(10), P. 105009 - 105009

Published: April 9, 2024

. Severe radiation-induced lymphopenia occurs in 40% of patients treated for primary brain tumors and is an independent risk factor poor survival outcomes. We developed

Language: Английский

Citations

6