The CD38 glycohydrolase and the NAD sink: implications for pathological conditions DOI
Julianna D. Zeidler, Kelly A. Hogan, Guillermo Agorrody

et al.

AJP Cell Physiology, Journal Year: 2022, Volume and Issue: 322(3), P. C521 - C545

Published: Feb. 9, 2022

Nicotinamide adenine dinucleotide (NAD) acts as a cofactor in several oxidation-reduction (redox) reactions and is substrate for number of nonredox enzymes. NAD fundamental to variety cellular processes including energy metabolism, cell signaling, epigenetics. homeostasis appears be paramount importance health span longevity, its dysregulation associated with multiple diseases. metabolism dynamic maintained by synthesis degradation. The enzyme CD38, one the main NAD-consuming enzymes, key component homeostasis. majority CD38 localized plasma membrane catalytic domain facing extracellular environment, likely purpose controlling systemic levels NAD. Several types express but expression predominates on endothelial cells immune capable infiltrating organs tissues. Here we review potential roles disease postulate ways which causes changes contributes pathophysiology conditions. Indeed, animal models development infectious diseases, autoimmune disorders, fibrosis, metabolic age-associated diseases cancer, heart disease, neurodegeneration are altered enzymatic activity. Many these conditions modified CD38-deficient mice or blocking NADase In play role, CD38-dependent decline often common denominator pathophysiology. Thus, understanding may open new avenues treatment human

Language: Английский

Sex Hormones in Acquired Immunity and Autoimmune Disease DOI Creative Commons
Vaishali R. Moulton

Frontiers in Immunology, Journal Year: 2018, Volume and Issue: 9

Published: Oct. 4, 2018

Women have stronger immune responses to infections and vaccination than men. Paradoxically, the response comes at a steep price, which is high incidence of autoimmune diseases in women. The reasons why women immunity higher autoimmunity are not clear. Besides gender, sex hormones contribute development activity system, accounting for differences gender-related responses. Both innate adaptive systems bear receptors respond hormonal cues. This review focuses on role particularly estrogen, response, health, disease with an emphasis systemic lupus erythematosus.

Language: Английский

Citations

510
Autoimmunity and organ damage in systemic lupus erythematosus DOI
George C. Tsokos

Nature Immunology, Journal Year: 2020, Volume and Issue: 21(6), P. 605 - 614

Published: May 4, 2020

Language: Английский

Citations

439
Th17 Cells and the IL-23/IL-17 Axis in the Pathogenesis of Periodontitis and Immune-Mediated Inflammatory Diseases DOI Open Access
Kübra Bunte, Thomas Beikler

International Journal of Molecular Sciences, Journal Year: 2019, Volume and Issue: 20(14), P. 3394 - 3394

Published: July 10, 2019

Innate immunity represents the semi-specific first line of defense and provides initial host response to tissue injury, trauma, pathogens. activates adaptive immunity, both act highly regulated together establish maintain homeostasis. Any dysregulation this interaction can result in chronic inflammation autoimmunity is thought be a major underlying cause initiation progression prevalent immune-mediated inflammatory diseases (IMIDs) such as psoriasis, rheumatoid arthritis, bowel among others, periodontitis. Th1 Th2 cells immune system are players pathogenesis IMIDs. In addition, Th17 cells, their key cytokine IL-17, IL-23 seem play pivotal roles. This review aims provide an overview current knowledge about differentiation role IL-17/IL-23 axis Moreover, it association these IMIDs with periodontitis briefly discusses therapeutic potential agents that modulate axis.

Language: Английский

Citations

413
Single-cell RNA-seq reveals cell type–specific molecular and genetic associations to lupus DOI
Richard K. Perez, M. Grace Gordon, Meena Subramaniam

et al.

Science, Journal Year: 2022, Volume and Issue: 376(6589)

Published: April 7, 2022

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease. Knowledge of circulating immune cell types and states associated with SLE remains incomplete. We profiled more than 1.2 million peripheral blood mononuclear cells (162 cases, 99 controls) multiplexed single-cell RNA sequencing (mux-seq). Cases exhibited elevated expression type 1 interferon-stimulated genes (ISGs) in monocytes, reduction naïve CD4

Language: Английский

Citations

317
Regulatory T cells in the treatment of disease DOI Open Access
Amir Sharabi, Maria Tsokos, Ying Ding

et al.

Nature Reviews Drug Discovery, Journal Year: 2018, Volume and Issue: 17(11), P. 823 - 844

Published: Oct. 12, 2018

Language: Английский

Citations

268
Mesenchymal stromal cell therapies: immunomodulatory properties and clinical progress DOI Creative Commons
Xiaomo Wu,

Ju Jiang,

Zhongkai Gu

et al.

Stem Cell Research & Therapy, Journal Year: 2020, Volume and Issue: 11(1)

Published: Aug. 8, 2020

Mesenchymal stromal cells (MSCs) are a subset of heterogeneous non-hematopoietic fibroblast-like that can differentiate into multiple lineages, such as chondrocytes, osteoblasts, adipocytes, myoblasts, and others. These multipotent MSCs be found in nearly all tissues but mostly located perivascular niches, playing significant role tissue repair regeneration. Additionally, interact with immune both innate adaptive systems, modulating responses enabling immunosuppression tolerance induction. Understanding the biology their roles clinical treatment is crucial for developing MSC-based cellular therapy variety pathological conditions. Here, we review progress study on mechanisms underlying immunomodulatory regenerative effects MSCs; update medical translation MSCs, focusing registration trials leading to regulatory approvals; discuss how improve therapeutic efficacy safety MSC applications future.

Language: Английский

Citations

239
CD38: An Immunomodulatory Molecule in Inflammation and Autoimmunity DOI Creative Commons
Zayda L. Piedra-Quintero, Zachary Wilson, Porfirio Nava

et al.

Frontiers in Immunology, Journal Year: 2020, Volume and Issue: 11

Published: Nov. 30, 2020

CD38 is a molecule that can act as an enzyme, with NAD-depleting and intracellular signaling activity, or receptor adhesive functions. be found expressed either on the cell surface, where it may face extracellular milieu cytosol, in compartments, such endoplasmic reticulum, nuclear membrane, mitochondria. The main expression of observed hematopoietic cells, some cell-type specific differences between mouse human. role immune cells ranges from modulating differentiation to effector functions during inflammation, regulate recruitment, cytokine release, NAD availability. In line appears also play critical inflammatory processes autoimmunity, although whether has pathogenic regulatory effects varies depending disease, cell, animal model analyzed. Given complexity physiology been difficult completely understand biology this autoimmune inflammation. review, we analyze current knowledge controversies regarding inflammation autoimmunity novel molecular tools clarify gaps field.

Language: Английский

Citations

221
Understanding the role of environmental factors in the development of systemic lupus erythematosus DOI
Christine G. Parks, Aline de Souza Espíndola Santos, Medha Barbhaiya

et al.

Best Practice & Research Clinical Rheumatology, Journal Year: 2017, Volume and Issue: 31(3), P. 306 - 320

Published: June 1, 2017

Language: Английский

Citations

190
Aberrant T Cell Signaling and Subsets in Systemic Lupus Erythematosus DOI Creative Commons
Takayuki Katsuyama, George C. Tsokos, Vaishali R. Moulton

et al.

Frontiers in Immunology, Journal Year: 2018, Volume and Issue: 9

Published: May 17, 2018

Systemic lupus erythematosus (SLE) is a chronic multi-organ debilitating autoimmune disease, which mainly afflicts women in the reproductive years. A complex interaction of genetics, environmental factors and hormones result breakdown immune tolerance to "self" leading damage destruction multiple organs, such as skin, joints, kidneys, heart brain. Both innate adaptive systems are critically involved misguided response against self-antigens. Dendritic cells, neutrophils, lymphoid cells important initiating antigen presentation propagating inflammation at peripheral tissue sites. Autoantibodies produced by B lymphocytes deposition vital organs contribute damage. T increasingly being recognized key contributors disease pathogenesis. CD4 follicular helper enable autoantibody production, inflammatory Th17 subsets promote inflammation, while defects regulatory lead unchecked responses. better understanding molecular including signaling events gene regulation underlying dysfunctional SLE necessary pave path for management, therapy, perhaps prevention this disease. In review, we focus on aberrations cell highlight therapeutic advances field.

Language: Английский

Citations

189
CD38 Is Robustly Induced in Human Macrophages and Monocytes in Inflammatory Conditions DOI Creative Commons
Stephanie A. Amici, Nicholas A. Young, Janiret Narvaez-Miranda

et al.

Frontiers in Immunology, Journal Year: 2018, Volume and Issue: 9

Published: July 10, 2018

Macrophages and their monocyte precursors mediate innate immune responses can promote a spectrum of phenotypes from pro-inflammatory to pro-resolving. Currently, there are few markers that allow for robust dissection macrophage phenotype. We recently identified CD38 as marker inflammatory macrophages in murine vitro vivo models. However, it is unknown whether plays similar and/or functional role human diseases. Here, we establish transcript protein robustly induced exposed LPS (±IFN-γ) stimuli, but not with the alternative stimulus, IL-4. Pharmacologic genetic loss-of-function significantly reduced secretion cytokines IL-6 IL-12p40 glycolytic activity primary macrophages. Finally, analyses systemic lupus erythematosus patients revealed that, while all monocytes express CD38, high expression non-classical subpopulation associated disease. These data consistent an monocytes.

Language: Английский

Citations

184