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Article ; Online: Sterols in asthma.

Guerau-de-Arellano, Mireia / Britt, Rodney D

2022 Volume 43, Issue 10, Page(s) 792–799

Abstract: While sterols regulate immune processes key to the pathogenesis of asthma, inhibition of sterols with statin drugs has shown conflicting results in human asthma. Here, a novel understanding of the impact of sterols on type 17 immune responses and asthma ... ...

Abstract	While sterols regulate immune processes key to the pathogenesis of asthma, inhibition of sterols with statin drugs has shown conflicting results in human asthma. Here, a novel understanding of the impact of sterols on type 17 immune responses and asthma lead us to hypothesize that sterols and statins may be relevant to severe asthma endotypes with neutrophil infiltration.
MeSH term(s)	Asthma ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Sterols
Chemical Substances	Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Sterols
Language	English
Publishing date	2022-08-27
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2036831-8
ISSN	1471-4981 ; 1471-4906
ISSN (online)	1471-4981
ISSN	1471-4906
DOI	10.1016/j.it.2022.08.003
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Article ; Online: Akt isoforms in the immune system.

Guerau-de-Arellano, Mireia / Piedra-Quintero, Zayda L / Tsichlis, Philip N

Frontiers in immunology

2022 Volume 13, Page(s) 990874

Abstract: Akt is a PI3K-activated serine-threonine kinase that exists in three distinct isoforms. Akt's expression in most immune cells, either at baseline or upon activation, reflects its importance in the immune system. While Akt is most highly expressed in ... ...

Abstract	Akt is a PI3K-activated serine-threonine kinase that exists in three distinct isoforms. Akt's expression in most immune cells, either at baseline or upon activation, reflects its importance in the immune system. While Akt is most highly expressed in innate immune cells, it plays crucial roles in both innate and adaptive immune cell development and/or effector functions. In this review, we explore what's known about the role of Akt in innate and adaptive immune cells. Wherever possible, we discuss the overlapping and distinct role of the three Akt isoforms, namely Akt1, Akt2, and Akt3, in immune cells.
MeSH term(s)	Cell Differentiation ; Immune System/metabolism ; Protein Isoforms/metabolism ; Proto-Oncogene Proteins c-akt/metabolism
Chemical Substances	Protein Isoforms ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1)
Language	English
Publishing date	2022-08-23
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.990874
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Article ; Online: PRMT5 Promotes Cyclin E1 and Cell Cycle Progression in CD4 Th1 Cells and Correlates With EAE Severity.

Amici, Stephanie A / Osman, Wissam / Guerau-de-Arellano, Mireia

Frontiers in immunology

2021 Volume 12, Page(s) 695947

Abstract: Multiple Sclerosis (MS) is a debilitating central nervous system disorder associated with inflammatory T cells. Activation and expansion of inflammatory T cells is thought to be behind MS relapses and influence disease severity. Protein arginine N- ... ...

Abstract	Multiple Sclerosis (MS) is a debilitating central nervous system disorder associated with inflammatory T cells. Activation and expansion of inflammatory T cells is thought to be behind MS relapses and influence disease severity. Protein arginine N-methyltransferase 5 (PRMT5) is a T cell activation-induced enzyme that symmetrically dimethylates proteins and promotes T cell proliferation. However, the mechanism behind PRMT5-mediated control of T cell proliferation and whether PRMT5 contributes to diseases severity is unclear. Here, we evaluated the role of PRMT5 on cyclin/cdk pairs and cell cycle progression, as well as PRMT5's link to disease severity in an animal model of relapsing-remitting MS. Treatment of T helper 1 (mTh1) cells with the selective PRMT5 inhibitor, HLCL65, arrested activation-induced T cell proliferation at the G1 stage of the cell cycle, suggesting PRMT5 promotes cell cycle progression in CD4
MeSH term(s)	Animals ; Cell Cycle ; Cell Proliferation ; Cyclin E/metabolism ; Cyclin-Dependent Kinase 2/metabolism ; Disease Progression ; Encephalomyelitis, Autoimmune, Experimental/enzymology ; Encephalomyelitis, Autoimmune, Experimental/immunology ; Encephalomyelitis, Autoimmune, Experimental/pathology ; Genes, T-Cell Receptor ; Mice, Transgenic ; Multiple Sclerosis, Relapsing-Remitting/enzymology ; Multiple Sclerosis, Relapsing-Remitting/immunology ; Multiple Sclerosis, Relapsing-Remitting/pathology ; Oncogene Proteins/metabolism ; Phosphorylation ; Protein-Arginine N-Methyltransferases/metabolism ; Retinoblastoma Protein/metabolism ; Severity of Illness Index ; Signal Transduction ; Th1 Cells/enzymology ; Th1 Cells/immunology ; Th1 Cells/pathology
Chemical Substances	CCNE1 protein, human ; Cyclin E ; Oncogene Proteins ; Retinoblastoma Protein ; Prmt5 protein, mouse (EC 2.1.1.319) ; Protein-Arginine N-Methyltransferases (EC 2.1.1.319) ; Cdk2 protein, mouse (EC 2.7.11.22) ; Cyclin-Dependent Kinase 2 (EC 2.7.11.22)
Language	English
Publishing date	2021-06-08
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.695947
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Article ; Online: PRMT5 Promotes T follicular helper Cell Differentiation and Germinal Center Responses during Influenza Virus Infection.

Read, Kaitlin A / Amici, Stephanie A / Farsi, Sadaf / Cutcliffe, Madeline / Lee, Bella / Lio, Chan-Wang Jerry / Wu, Hsin-Jung Joyce / Guerau-de-Arellano, Mireia / Oestreich, Kenneth J

Journal of immunology (Baltimore, Md. : 1950)

2024 Volume 212, Issue 9, Page(s) 1442–1449

Abstract: Protein arginine methyltransferases (PRMTs) modify diverse protein targets and regulate numerous cellular processes; yet, their contributions to individual effector T cell responses during infections are incompletely understood. In this study, we ... ...

Abstract	Protein arginine methyltransferases (PRMTs) modify diverse protein targets and regulate numerous cellular processes; yet, their contributions to individual effector T cell responses during infections are incompletely understood. In this study, we identify PRMT5 as a critical regulator of CD4+ T follicular helper cell (Tfh) responses during influenza virus infection in mice. Conditional PRMT5 deletion in murine T cells results in an almost complete ablation of both Tfh and T follicular regulatory populations and, consequently, reduced B cell activation and influenza-specific Ab production. Supporting a potential mechanism, we observe elevated surface expression of IL-2Rα on non-T regulatory effector PRMT5-deficient T cells. Notably, IL-2 signaling is known to negatively impact Tfh differentiation. Collectively, our findings identify PRMT5 as a prominent regulator of Tfh programming, with potential causal links to IL-2 signaling.
MeSH term(s)	Mice ; Animals ; Humans ; Interleukin-2/metabolism ; T-Lymphocytes, Helper-Inducer/metabolism ; T Follicular Helper Cells ; Influenza, Human ; Cell Differentiation ; Germinal Center ; Orthomyxoviridae ; Orthomyxoviridae Infections/metabolism
Chemical Substances	Interleukin-2
Language	English
Publishing date	2024-03-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.2300270
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Article ; Online: Sterols and immune mechanisms in asthma.

Britt, Rodney D / Porter, Ned / Grayson, Mitchell H / Gowdy, Kymberly M / Ballinger, Megan / Wada, Kara / Kim, Hye-Young / Guerau-de-Arellano, Mireia

The Journal of allergy and clinical immunology

2022 Volume 151, Issue 1, Page(s) 47–59

Abstract: The field of sterol and oxysterol biology in lung disease has recently gained attention, revealing a unique need for sterol uptake and metabolism in the lung. The presence of cholesterol transport, biosynthesis, and sterol/oxysterol-mediated signaling in ...

Abstract	The field of sterol and oxysterol biology in lung disease has recently gained attention, revealing a unique need for sterol uptake and metabolism in the lung. The presence of cholesterol transport, biosynthesis, and sterol/oxysterol-mediated signaling in immune cells suggests a role in immune regulation. In support of this idea, statin drugs that inhibit the cholesterol biosynthesis rate-limiting step enzyme, hydroxymethyl glutaryl coenzyme A reductase, show immunomodulatory activity in several models of inflammation. Studies in human asthma reveal contradicting results, whereas promising retrospective studies suggest benefits of statins in severe asthma. Here, we provide a timely review by discussing the role of sterols in immune responses in asthma, analytical tools to evaluate the role of sterols in disease, and potential mechanistic pathways and targets relevant to asthma. Our review reveals the importance of sterols in immune processes and highlights the need for further research to solve critical gaps in the field.
MeSH term(s)	Humans ; Sterols/metabolism ; Retrospective Studies ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology ; Asthma ; Cholesterol ; Oxysterols
Chemical Substances	Sterols ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Cholesterol (97C5T2UQ7J) ; Oxysterols
Language	English
Publishing date	2022-10-29
Publishing country	United States
Document type	Review ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	121011-7
ISSN	1097-6825 ; 1085-8725 ; 0091-6749
ISSN (online)	1097-6825 ; 1085-8725
ISSN	0091-6749
DOI	10.1016/j.jaci.2022.09.025
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Article ; Online: The Minority Scientists' Experience: Challenging and Overcoming Barriers to Enhancing Diversity and Career Advancement.

Webb, Tonya J / Guerau-de-Arellano, Mireia / Jones, Harlan P / Butts, Cherié L / Sanchez-Perez, Luis / Montaner, Luis J

Journal of immunology (Baltimore, Md. : 1950)

2022 Volume 208, Issue 2, Page(s) 197–202

Abstract: Minority groups face barriers in accessing quality health care, professional advancement, and representation in immunology research efforts as a result of institutional racism that if unaddressed can perpetuate a lack of diversity. In 2021, the AAI ... ...

Abstract	Minority groups face barriers in accessing quality health care, professional advancement, and representation in immunology research efforts as a result of institutional racism that if unaddressed can perpetuate a lack of diversity. In 2021, the AAI Minority Affairs Committee convened a cross section of academic and industry scientists from underrepresented groups at various stages of their professions to discuss how best to address the toll racism takes on study design and scientific careers. Panelists drew directly from their own experiences as scientists to share perspectives and strategies for countering a lack of representation in clinical research, responding to microaggressions, navigating academic advancement, and providing effective mentorship. The session reinforced the need for minority scientists to take an active role in advocating for diversity, engaging mentors, and taking responsibility to face rather than avoid institutional obstacles. Overall, increased dialogue and institutional awareness of the experience of scientists from underrepresented groups in research remain the best tools to ensure a health equity mindset and advancement of their careers.
MeSH term(s)	Academic Success ; Biomedical Research ; Career Mobility ; Cultural Diversity ; Humans ; Mentoring ; Mentors ; Microaggression ; Minority Groups/statistics & numerical data ; Research Personnel/statistics & numerical data ; Sexual and Gender Minorities/statistics & numerical data ; Systemic Racism/statistics & numerical data
Language	English
Publishing date	2022-01-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.2101077
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Article ; Online: CD38: An Immunomodulatory Molecule in Inflammation and Autoimmunity.

Piedra-Quintero, Zayda L / Wilson, Zachary / Nava, Porfirio / Guerau-de-Arellano, Mireia

Frontiers in immunology

2020 Volume 11, Page(s) 597959

Abstract: CD38 is a molecule that can act as an enzyme, with NAD-depleting and intracellular signaling activity, or as a receptor with adhesive functions. CD38 can be found expressed either on the cell surface, where it may face the extracellular milieu or the ... ...

Abstract	CD38 is a molecule that can act as an enzyme, with NAD-depleting and intracellular signaling activity, or as a receptor with adhesive functions. CD38 can be found expressed either on the cell surface, where it may face the extracellular milieu or the cytosol, or in intracellular compartments, such as endoplasmic reticulum, nuclear membrane, and mitochondria. The main expression of CD38 is observed in hematopoietic cells, with some cell-type specific differences between mouse and human. The role of CD38 in immune cells ranges from modulating cell differentiation to effector functions during inflammation, where CD38 may regulate cell recruitment, cytokine release, and NAD availability. In line with a role in inflammation, CD38 appears to also play a critical role in inflammatory processes during autoimmunity, although whether CD38 has pathogenic or regulatory effects varies depending on the disease, immune cell, or animal model analyzed. Given the complexity of the physiology of CD38 it has been difficult to completely understand the biology of this molecule during autoimmune inflammation. In this review, we analyze current knowledge and controversies regarding the role of CD38 during inflammation and autoimmunity and novel molecular tools that may clarify current gaps in the field.
MeSH term(s)	ADP-ribosyl Cyclase 1/chemistry ; ADP-ribosyl Cyclase 1/genetics ; ADP-ribosyl Cyclase 1/metabolism ; Animals ; Antigen Presentation/immunology ; Autoimmunity ; Biomarkers ; Cell Movement ; Cytokines/metabolism ; Disease Susceptibility ; Gene Expression Regulation ; Humans ; Immunomodulation ; Inflammation/etiology ; Inflammation/metabolism ; Membrane Glycoproteins/chemistry ; Membrane Glycoproteins/genetics ; Membrane Glycoproteins/metabolism ; Phagocytosis ; Protein Transport
Chemical Substances	Biomarkers ; Cytokines ; Membrane Glycoproteins ; CD38 protein, human (EC 3.2.2.5) ; ADP-ribosyl Cyclase 1 (EC 3.2.2.6)
Language	English
Publishing date	2020-11-30
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2020.597959
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Article ; Online: Protein Arginine Methyltransferase 5 in T Lymphocyte Biology.

Sengupta, Shouvonik / Kennemer, Austin / Patrick, Kristin / Tsichlis, Philip / Guerau-de-Arellano, Mireia

Trends in immunology

2020 Volume 41, Issue 10, Page(s) 918–931

Abstract: Protein arginine methyltransferase 5 (PRMT5) is the major methyltransferase (MT) catalyzing symmetric dimethylation (SDM). PRMT5 regulates developmental, homeostatic and disease processes in vertebrates and invertebrates, and a carcinogenic role has been ...

Abstract	Protein arginine methyltransferase 5 (PRMT5) is the major methyltransferase (MT) catalyzing symmetric dimethylation (SDM). PRMT5 regulates developmental, homeostatic and disease processes in vertebrates and invertebrates, and a carcinogenic role has been observed in mammals. Recently, tools generated for PRMT5 loss of function have allowed researchers to demonstrate essential roles for PRMT5 in mouse and human lymphocyte biology. PRMT5 modulates CD4
MeSH term(s)	Animals ; Cell Differentiation/genetics ; Humans ; Protein-Arginine N-Methyltransferases/immunology ; T-Lymphocytes/enzymology ; T-Lymphocytes/immunology ; Th17 Cells/enzymology
Chemical Substances	Protein-Arginine N-Methyltransferases (EC 2.1.1.319)
Language	English
Publishing date	2020-09-02
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2036831-8
ISSN	1471-4981 ; 1471-4906
ISSN (online)	1471-4981
ISSN	1471-4906
DOI	10.1016/j.it.2020.08.007
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Article ; Online: Emerging Role for Methylation in Multiple Sclerosis: Beyond DNA.

Webb, Lindsay M / Guerau-de-Arellano, Mireia

Trends in molecular medicine

2017 Volume 23, Issue 6, Page(s) 546–562

Abstract: Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system. The inflammatory and neurodegenerative pathways driving MS are modulated by DNA, lysine, and arginine methylation, as evidenced by studies made possible by novel ... ...

Abstract	Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system. The inflammatory and neurodegenerative pathways driving MS are modulated by DNA, lysine, and arginine methylation, as evidenced by studies made possible by novel tools for methylation detection or loss of function. We present evidence that MS is associated with genetic variants and metabolic changes that impact on methylation. Further, we comprehensively review current understanding of how methylation can impact on central nervous system (CNS) resilience and neuroregenerative potential, as well as inflammatory versus regulatory T helper (Th) cell balance. These findings are discussed in the context of therapeutic relevance for MS, with broad implications in other neurologic and immune-mediated diseases.
Language	English
Publishing date	2017-06
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2036490-8
ISSN	1471-499X ; 1471-4914
ISSN (online)	1471-499X
ISSN	1471-4914
DOI	10.1016/j.molmed.2017.04.004
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Article: Molecular Mechanisms Modulating the Phenotype of Macrophages and Microglia.

Amici, Stephanie A / Dong, Joycelyn / Guerau-de-Arellano, Mireia

Frontiers in immunology

2017 Volume 8, Page(s) 1520

Abstract: Macrophages and microglia play crucial roles during central nervous system development, homeostasis and acute events such as infection or injury. The diverse functions of tissue macrophages and microglia are mirrored by equally diverse phenotypes. A ... ...

Abstract	Macrophages and microglia play crucial roles during central nervous system development, homeostasis and acute events such as infection or injury. The diverse functions of tissue macrophages and microglia are mirrored by equally diverse phenotypes. A model of inflammatory/M1 versus a resolution phase/M2 macrophages has been widely used. However, the complexity of macrophage function can only be achieved by the existence of varied, plastic and tridimensional macrophage phenotypes. Understanding how tissue macrophages integrate environmental signals
Language	English
Publishing date	2017-11-10
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2606827-8
ISSN	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2017.01520
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