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1.
Annu Rev Immunol ; 42(1): 207-233, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38211945

RESUMO

The immune system and the kidneys are closely related. Immune components mediate acute kidney disease and are crucial to the progression of chronic kidney disease. Beyond its pathogenic functions, the immune system supports immunological homeostasis in healthy kidneys. The kidneys help maintain immune equilibrium by removing metabolic waste products and toxins, thereby limiting local and systemic inflammation. In this review, we describe the close relationship between the immune system and the kidneys. We discuss how the imbalance in the immune response can be deleterious to the kidneys and how immunomodulation can be important in preventing end-stage renal disease. In addition, recent tools such as in silico platforms and kidney organoids can help unveil the relationship between immune cells and kidney homeostasis.


Assuntos
Nefropatias , Humanos , Animais , Nefropatias/imunologia , Nefropatias/etiologia , Nefropatias/metabolismo , Rim/imunologia , Rim/metabolismo , Homeostase , Imunomodulação , Suscetibilidade a Doenças
2.
Annu Rev Immunol ; 42(1): 57-81, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37989144

RESUMO

Barrier tissues are highly innervated by sensory and autonomic nerves that are positioned in close proximity to both stromal and immune cell populations. Together with a growing awareness of the far-reaching consequences of neuroimmune interactions, recent studies have uncovered key mechanisms through which they contribute to organ homeostasis and immunity. It has also become clear that dysregulation of such interactions is implicated in the development of chronic lung diseases. This review describes the characteristics of the lung nervous system and discusses the molecular mechanisms that underlie lung neuroimmune interactions in infection and disease. We have contextualized the current literature and identified opportune areas for further investigation. Indeed, both the lung-brain axis and local neuroimmune interactions hold enormous potential for the exploration and development of novel therapeutic strategies targeting lung diseases.


Assuntos
Pulmão , Neuroimunomodulação , Humanos , Animais , Pulmão/imunologia , Pneumopatias/imunologia , Pneumopatias/etiologia , Encéfalo/imunologia , Encéfalo/fisiologia
3.
Annu Rev Immunol ; 42(1): 551-584, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38941604

RESUMO

Poxviruses have evolved a wide array of mechanisms to evade the immune response, and we provide an overview of the different immunomodulatory strategies. Poxviruses prevent the recognition of viral DNA that triggers the immune responses and inhibit signaling pathways within the infected cell. A unique feature of poxviruses is the production of secreted proteins that mimic cytokines and cytokine receptors, acting as decoy receptors to neutralize the activity of cytokines and chemokines. The capacity of these proteins to evade cellular immune responses by inhibiting cytokine activation is complemented by poxviruses' strategies to block natural killer cells and cytotoxic T cells, often through interfering with antigen presentation pathways. Mechanisms that target complement activation are also encoded by poxviruses. Virus-encoded proteins that target immune molecules and pathways play a major role in immune modulation, and their contribution to viral pathogenesis, facilitating virus replication or preventing immunopathology, is discussed.


Assuntos
Evasão da Resposta Imune , Infecções por Poxviridae , Poxviridae , Humanos , Poxviridae/imunologia , Poxviridae/fisiologia , Animais , Infecções por Poxviridae/imunologia , Citocinas/metabolismo , Transdução de Sinais , Proteínas Virais/metabolismo , Proteínas Virais/imunologia , Apresentação de Antígeno/imunologia , Interações Hospedeiro-Patógeno/imunologia
4.
Annu Rev Immunol ; 42(1): 317-345, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38941605

RESUMO

Regionalized immune surveillance relies on the concerted efforts of diverse memory T cell populations. Of these, tissue-resident memory T (TRM) cells are strategically positioned in barrier tissues, where they enable efficient frontline defense against infections and cancer. However, the long-term persistence of these cells has been implicated in a variety of immune-mediated pathologies. Consequently, modulating TRM cell populations represents an attractive strategy for novel vaccination and therapeutic interventions against tissue-based diseases. Here, we provide an updated overview of TRM cell heterogeneity and function across tissues and disease states. We discuss mechanisms of TRM cell-mediated immune protection and their potential contributions to autoimmune disorders. Finally, we examine how TRM cell responses might be durably boosted or dampened for therapeutic gain.


Assuntos
Memória Imunológica , Células T de Memória , Humanos , Animais , Células T de Memória/imunologia , Células T de Memória/metabolismo , Doenças Autoimunes/imunologia , Doenças Autoimunes/terapia , Especificidade de Órgãos/imunologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Vigilância Imunológica
5.
Annu Rev Immunol ; 42(1): 83-102, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38941606

RESUMO

Circadian rhythms of approximately 24 h have emerged as important modulators of the immune system. These oscillations are important for mounting short-term, innate immune responses, but surprisingly also long-term, adaptive immune responses. Recent data indicate that they play a central role in antitumor immunity, in both mice and humans. In this review, we discuss the evolving literature on circadian antitumor immune responses and the underlying mechanisms that control them. We further provide an overview of circadian treatment regimens-chrono-immunotherapies-that harness time-of-day differences in immunity for optimal efficacy. Our aim is to provide an overview for researchers and clinicians alike, for a better understanding of the circadian immune system and how to best harness it for chronotherapeutic interventions. This knowledge is important for a better understanding of immune responses per se and could revolutionize the way we approach the treatment of cancer and a range of other diseases, ultimately improving clinical practice.


Assuntos
Ritmo Circadiano , Neoplasias , Humanos , Ritmo Circadiano/imunologia , Animais , Neoplasias/imunologia , Neoplasias/terapia , Imunoterapia/métodos , Imunidade Inata , Imunidade Adaptativa
6.
Annu Rev Immunol ; 42(1): 289-316, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38277691

RESUMO

The intestinal epithelium, which segregates the highly stimulatory lumen from the underlying tissue, harbors one of the largest lymphocyte populations in the body, intestinal intraepithelial lymphocytes (IELs). IELs must balance tolerance, resistance, and tissue protection to maintain epithelial homeostasis and barrier integrity. This review discusses the ontogeny, environmental imprinting, T cell receptor (TCR) repertoire, and function of intestinal IELs. Despite distinct developmental pathways, IEL subsets share core traits including an epithelium-adapted profile, innate-like properties, cytotoxic potential, and limited TCR diversity. IELs also receive important developmental and functional cues through interactions with epithelial cells, microbiota, and dietary components. The restricted TCR diversity of IELs suggests that a limited set of intestinal antigens drives IEL responses, with potential functional consequences. Finally, IELs play a key role in promoting homeostatic immunity and epithelial barrier integrity but can become pathogenic upon dysregulation. Therefore, IELs represent intriguing but underexamined therapeutic targets for inflammatory diseases and cancer.


Assuntos
Mucosa Intestinal , Linfócitos Intraepiteliais , Humanos , Animais , Linfócitos Intraepiteliais/imunologia , Linfócitos Intraepiteliais/metabolismo , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Homeostase , Receptores de Antígenos de Linfócitos T/metabolismo , Intestinos/imunologia
7.
Annu Rev Immunol ; 42(1): 647-677, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38424658

RESUMO

Lymphocytes spanning the entire innate-adaptive spectrum can stably reside in tissues and constitute an integral component of the local defense network against immunological challenges. In tight interactions with the epithelium and endothelium, tissue-resident lymphocytes sense antigens and alarmins elicited by infectious microbes and abiotic stresses at barrier sites and mount effector responses to restore tissue homeostasis. Of note, such a host cell-directed immune defense system has been recently demonstrated to surveil epithelial cell transformation and carcinoma development, as well as cancer cell metastasis at selected distant organs, and thus represents a primordial cancer immune defense module. Here we review how distinct lineages of tissue-resident innate lymphoid cells, innate-like T cells, and adaptive T cells participate in a form of multilayered cancer immunity in murine models and patients, and how their convergent effector programs may be targeted through both shared and private regulatory pathways for cancer immunotherapy.


Assuntos
Imunidade Inata , Neoplasias , Humanos , Animais , Neoplasias/imunologia , Neoplasias/terapia , Linfócitos/imunologia , Linfócitos/metabolismo , Microambiente Tumoral/imunologia , Imunidade Adaptativa , Imunoterapia/métodos
8.
Annu Rev Immunol ; 42(1): 375-399, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38360545

RESUMO

The liver's unique characteristics have a profound impact on the priming and maintenance of adaptive immunity. This review delves into the cellular circuits that regulate adaptive immune responses in the liver, with a specific focus on hepatitis B virus infection as an illustrative example. A key aspect highlighted is the liver's specialized role in priming CD8+ T cells, leading to a distinct state of immune hyporesponsiveness. Additionally, the influence of the liver's hemodynamics and anatomical features, particularly during liver fibrosis and cirrhosis, on the differentiation and function of adaptive immune cells is discussed. While the primary emphasis is on CD8+ T cells, recent findings regarding the involvement of B cells and CD4+ T cells in hepatic immunity are also reviewed. Furthermore, we address the challenges ahead and propose integrating cutting-edge techniques, such as spatial biology, and combining mouse models with human sample analyses to gain comprehensive insights into the liver's adaptive immunity. This understanding could pave the way for novel therapeutic strategies targeting infectious diseases, malignancies, and inflammatory liver conditions like metabolic dysfunction-associated steatohepatitis and autoimmune hepatitis.


Assuntos
Imunidade Adaptativa , Fígado , Humanos , Animais , Fígado/imunologia , Fígado/metabolismo , Fígado/patologia , Linfócitos T CD8-Positivos/imunologia , Vírus da Hepatite B/imunologia , Vírus da Hepatite B/fisiologia , Hepatite B/imunologia , Linfócitos B/imunologia , Linfócitos B/metabolismo , Linfócitos T CD4-Positivos/imunologia
9.
Annu Rev Immunol ; 42(1): 401-425, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38360544

RESUMO

IgE-mediated food allergy (IgE-FA) occurs due to a breakdown in immune tolerance that leads to a detrimental type 2 helper T cell (TH2) adaptive immune response. While the processes governing this loss of tolerance are incompletely understood, several host-related and environmental factors impacting the risk of IgE-FA development have been identified. Mounting evidence supports the role of an impaired epithelial barrier in the development of IgE-FA, with exposure of allergens through damaged skin and gut epithelium leading to the aberrant production of alarmins and activation of TH2-type allergic inflammation. The treatment of IgE-FA has historically been avoidance with acute management of allergic reactions, but advances in allergen-specific immunotherapy and the development of biologics and other novel therapeutics are rapidly changing the landscape of food allergy treatment. Here, we discuss the pathogenesis and immunobiology of IgE-FA in addition to its diagnosis, prognosis, and treatment.


Assuntos
Alérgenos , Hipersensibilidade Alimentar , Imunoglobulina E , Humanos , Hipersensibilidade Alimentar/terapia , Hipersensibilidade Alimentar/imunologia , Animais , Imunoglobulina E/imunologia , Imunoglobulina E/metabolismo , Alérgenos/imunologia , Dessensibilização Imunológica/métodos , Células Th2/imunologia , Tolerância Imunológica , Suscetibilidade a Doenças
10.
Annu Rev Immunol ; 42(1): 427-53, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38360547

RESUMO

The role of the autoimmune regulator (Aire) in central immune tolerance and thymic self-representation was first described more than 20 years ago, but fascinating new insights into its biology continue to emerge, particularly in the era of advanced single-cell genomics. We briefly describe the role of human genetics in the discovery of Aire, as well as insights into its function gained from genotype-phenotype correlations and the spectrum of Aire-associated autoimmunity-including insights from patients with Aire mutations with broad and diverse implications for human health. We then highlight emerging trends in Aire biology, focusing on three topic areas. First, we discuss medullary thymic epithelial diversity and the role of Aire in thymic epithelial development. Second, we highlight recent developments regarding the molecular mechanisms of Aire and its binding partners. Finally, we describe the rapidly evolving biology of the identity and function of extrathymic Aire-expressing cells (eTACs), and a novel eTAC subset called Janus cells, as well as their potential roles in immune homeostasis.


Assuntos
Proteína AIRE , Autoimunidade , Fatores de Transcrição , Humanos , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Animais , Timo/imunologia , Timo/metabolismo , Mutação , Tolerância Imunológica , Células Epiteliais/metabolismo , Células Epiteliais/imunologia , Doenças Autoimunes/imunologia , Doenças Autoimunes/genética , Doenças Autoimunes/metabolismo
11.
Annu Rev Immunol ; 42(1): 1-20, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37788477

RESUMO

I have spent more than the last 40 years at the University of California, San Francisco (UCSF), studying T cell receptor (TCR) signaling. I was blessed with supportive mentors, an exceptionally talented group of trainees, and wonderful collaborators and colleagues during my journey who have enabled me to make significant contributions to our understanding of how the TCR initiates signaling. TCR signaling events contribute to T cell development as well as to mature T cell activation and differentiation.


Assuntos
Ativação Linfocitária , Receptores de Antígenos de Linfócitos T , Transdução de Sinais , Linfócitos T , Receptores de Antígenos de Linfócitos T/metabolismo , Humanos , Animais , Linfócitos T/imunologia , Linfócitos T/metabolismo , História do Século XX , História do Século XXI , Diferenciação Celular
12.
Annu Rev Immunol ; 42(1): 153-178, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38941602

RESUMO

The intestine is the largest peripheral lymphoid organ in animals, including humans, and interacts with a vast array of microorganisms called the gut microbiota. Comprehending the symbiotic relationship between the gut microbiota and our immune system is essential not only for the field of immunology but also for understanding the pathogenesis of various systemic diseases, including cancer, cardiometabolic disorders, and extraintestinal autoimmune conditions. Whereas microbe-derived antigens are crucial for activating the intestinal immune system, particularly T and B cells, as environmental cues, microbes and their metabolites play a critical role in directing the differentiation of these immune cells. Microbial metabolites are regarded as messengers from the gut microbiota, since bacteria have the ability to produce unique molecules that humans cannot, and many immune cells in the intestine express receptors for these molecules. This review highlights the distinct relationships between microbial metabolites and the differentiation and function of the immune system.


Assuntos
Microbioma Gastrointestinal , Humanos , Animais , Microbioma Gastrointestinal/imunologia , Diferenciação Celular , Linfócitos B/imunologia , Linfócitos B/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismo , Bactérias/imunologia , Bactérias/metabolismo
13.
Annu Rev Immunol ; 42(1): 489-519, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38941607

RESUMO

Recent advances have contributed to a mechanistic understanding of neuroimmune interactions in the intestine and revealed an essential role of this cross talk for gut homeostasis and modulation of inflammatory and infectious intestinal diseases. In this review, we describe the innervation of the intestine by intrinsic and extrinsic neurons and then focus on the bidirectional communication between neurons and immune cells. First, we highlight the contribution of neuronal subtypes to the development of colitis and discuss the different immune and epithelial cell types that are regulated by neurons via the release of neuropeptides and neurotransmitters. Next, we review the role of intestinal inflammation in the development of visceral hypersensitivity and summarize how inflammatory mediators induce peripheral and central sensitization of gut-innervating sensory neurons. Finally, we outline the importance of immune cells and gut microbiota for the survival and function of different neuronal populations at homeostasis and during bacterial and helminth infection.


Assuntos
Neuroimunomodulação , Humanos , Animais , Intestinos/imunologia , Homeostase , Microbioma Gastrointestinal/imunologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Neurônios/metabolismo , Neurônios/imunologia , Neuropeptídeos/metabolismo , Sistema Nervoso Entérico/imunologia , Sistema Nervoso Entérico/metabolismo
14.
Annu Rev Immunol ; 42(1): 259-288, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38277692

RESUMO

Gastrointestinal nematode (GIN) infection has applied significant evolutionary pressure to the mammalian immune system and remains a global economic and human health burden. Upon infection, type 2 immune sentinels activate a common antihelminth response that mobilizes and remodels the intestinal tissue for effector function; however, there is growing appreciation of the impact GIN infection also has on the distal tissue immune state. Indeed, this effect is observed even in tissues through which GINs never transit. This review highlights how GIN infection modulates systemic immunity through (a) induction of host resistance and tolerance responses, (b) secretion of immunomodulatory products, and (c) interaction with the intestinal microbiome. It also discusses the direct consequences that changes to distal tissue immunity can have for concurrent and subsequent infection, chronic noncommunicable diseases, and vaccination efficacy.


Assuntos
Microbioma Gastrointestinal , Nematoides , Infecções por Nematoides , Animais , Humanos , Infecções por Nematoides/imunologia , Nematoides/imunologia , Nematoides/fisiologia , Microbioma Gastrointestinal/imunologia , Imunomodulação , Interações Hospedeiro-Parasita/imunologia , Enteropatias Parasitárias/imunologia , Tolerância Imunológica , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/parasitologia
15.
Annu Rev Immunol ; 42(1): 179-206, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38166256

RESUMO

T cell responses must be balanced to ensure adequate protection against malignant transformation and an array of pathogens while also limiting damage to healthy cells and preventing autoimmunity. T cell exhaustion serves as a regulatory mechanism to limit the activity and effector function of T cells undergoing chronic antigen stimulation. Exhausted T cells exhibit poor proliferative potential; high inhibitory receptor expression; altered transcriptome, epigenome, and metabolism; and, most importantly, reduced effector function. While exhaustion helps to restrain damage caused by aberrant T cells in settings of autoimmune disease, it also limits the ability of cells to respond against persistent infection and cancer, leading to disease progression. Here we review the process of T cell exhaustion, detailing the key characteristics and drivers as well as highlighting our current understanding of the underlying transcriptional and epigenetic programming. We also discuss how exhaustion can be targeted to enhance T cell functionality in cancer.


Assuntos
Neoplasias , Linfócitos T , Humanos , Animais , Neoplasias/imunologia , Neoplasias/etiologia , Neoplasias/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismo , Epigênese Genética , Ativação Linfocitária/imunologia , Doenças Autoimunes/imunologia , Doenças Autoimunes/metabolismo , Exaustão das Células T
16.
Annu Rev Immunol ; 42(1): 103-126, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38011889

RESUMO

Autoimmune diseases with B cell-directed therapeutics approved by the US Food and Drug Administration are surprisingly diverse in clinical manifestations and pathophysiology. In this review, we focus on recent clinical and mechanistic insights into the efficacy of B cell depletion in these diverse autoimmune disorders, the rapidly expanding armamentarium of approved agents, and future approaches. The pathogenic roles for B cells include direct functions such as production of autoantibodies and proinflammatory cytokines and indirect functions via antigen presentation to T cells. The efficacy of B cell-depleting strategies varies across diseases and likely reflects the complexity of disease pathogenesis and relative contribution of B cell roles. Additionally, B cell-depleting therapies do not equally target all B cell subsets in all patients, and this likely explains some of the variability in responses. Recent reports of B cell depletion with novel chimeric antigen receptor (CAR) T cell approaches in an expanding number of autoimmune diseases highlight the potential role of B cell depletion in resetting immune tolerance. The relative importance of eliminating autoreactive B cells and plasma cells and approaches to doing so will also be discussed.


Assuntos
Doenças Autoimunes , Autoimunidade , Linfócitos B , Humanos , Doenças Autoimunes/terapia , Doenças Autoimunes/imunologia , Linfócitos B/imunologia , Linfócitos B/metabolismo , Animais , Depleção Linfocítica , Imunoterapia Adotiva/métodos , Tolerância Imunológica , Autoanticorpos/imunologia , Autoanticorpos/metabolismo , Receptores de Antígenos Quiméricos/metabolismo , Receptores de Antígenos Quiméricos/imunologia , Receptores de Antígenos Quiméricos/genética
17.
Annu Rev Immunol ; 42(1): 35-55, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37906942

RESUMO

The kidneys are life-sustaining organs that are vital to removing waste from our bodies. Because of their anatomic position and high blood flow, the kidneys are vulnerable to damage due to infections and autoinflammatory conditions. Even now, our knowledge of immune responses in the kidney is surprisingly rudimentary. Studying kidney-specific immune events is challenging because of the poor regenerative capacity of the nephrons, accumulation of uremic toxins, and hypoxia- and arterial blood pressure-mediated changes, all of which have unexpected positive or negative impacts on the immune response in the kidney. Kidney-specific defense confers protection against pathogens. On the other hand, unresolved inflammation leads to kidney damage and fibrosis. Interleukin-17 is a proinflammatory cytokine that has been linked to immunity against pathogens and pathogenesis of autoinflammatory diseases. In this review, we discuss current knowledge of IL-17 activities in the kidney in the context of infections, autoinflammatory diseases, and renal fibrosis.


Assuntos
Infecções , Interleucina-17 , Rim , Animais , Humanos , Fibrose , Infecções/imunologia , Infecções/etiologia , Inflamação/imunologia , Inflamação/metabolismo , Interleucina-17/metabolismo , Rim/imunologia , Rim/metabolismo , Rim/patologia , Nefropatias/etiologia , Nefropatias/metabolismo , Nefropatias/imunologia
18.
Annu Rev Immunol ; 42(1): 21-33, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37827174

RESUMO

Elite controllers are a heterogeneous group of people living with HIV who control viral replication without antiretroviral therapy. There is substantial evidence that at least some elite controllers are infected with replication-competent virus, thus they may serve as a model of a functional cure of HIV. The mechanisms responsible for virologic control have been actively studied. The most objective data support CD8+ T cell-based mechanisms of control, but other immune responses, mediated by antibodies and natural killer cells, may also play a role in controlling viral replication. In this article, we review the evidence for different mechanisms of immune control in these remarkable individuals.


Assuntos
Infecções por HIV , Células Matadoras Naturais , Replicação Viral , Humanos , Infecções por HIV/imunologia , Infecções por HIV/virologia , Infecções por HIV/tratamento farmacológico , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , HIV-1/imunologia , HIV-1/fisiologia , Animais
19.
Annu Rev Immunol ; 42(1): 615-645, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38941608

RESUMO

The COVID-19 pandemic was caused by the recently emerged ß-coronavirus SARS-CoV-2. SARS-CoV-2 has had a catastrophic impact, resulting in nearly 7 million fatalities worldwide to date. The innate immune system is the first line of defense against infections, including the detection and response to SARS-CoV-2. Here, we discuss the innate immune mechanisms that sense coronaviruses, with a focus on SARS-CoV-2 infection and how these protective responses can become detrimental in severe cases of COVID-19, contributing to cytokine storm, inflammation, long-COVID, and other complications. We also highlight the complex cross talk among cytokines and the cellular components of the innate immune system, which can aid in viral clearance but also contribute to inflammatory cell death, cytokine storm, and organ damage in severe COVID-19 pathogenesis. Furthermore, we discuss how SARS-CoV-2 evades key protective innate immune mechanisms to enhance its virulence and pathogenicity, as well as how innate immunity can be therapeutically targeted as part of the vaccination and treatment strategy. Overall, we highlight how a comprehensive understanding of innate immune mechanisms has been crucial in the fight against SARS-CoV-2 infections and the development of novel host-directed immunotherapeutic strategies for various diseases.


Assuntos
COVID-19 , Imunidade Inata , SARS-CoV-2 , Humanos , COVID-19/imunologia , SARS-CoV-2/imunologia , SARS-CoV-2/fisiologia , Síndrome da Liberação de Citocina/imunologia , Citocinas/metabolismo , Animais , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Infecções por Coronavirus/prevenção & controle , Evasão da Resposta Imune
20.
Annu Rev Immunol ; 42(1): 235-258, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38271641

RESUMO

The choice of developing thymocytes to become CD8+ cytotoxic or CD4+ helper T cells has been intensely studied, but many of the underlying mechanisms remain to be elucidated. Recent multiomics approaches have provided much higher resolution analysis of gene expression in developing thymocytes than was previously achievable, thereby offering a fresh perspective on this question. Focusing on our recent studies using CITE-seq (cellular indexing of transcriptomes and epitopes) analyses of mouse thymocytes, we present a detailed timeline of RNA and protein expression changes during CD8 versus CD4 T cell differentiation. We also revisit our current understanding of the links between T cell receptor signaling and expression of the lineage-defining transcription factors ThPOK and RUNX3. Finally, we propose a sequential selection model to explain the tight linkage between MHC-I versus MHC-II recognition and T cell lineage choice. This model incorporates key aspects of previously proposed kinetic signaling, instructive, and stochastic/selection models.


Assuntos
Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Diferenciação Celular , Linhagem da Célula , Animais , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Humanos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Receptores de Antígenos de Linfócitos T/metabolismo , Transdução de Sinais , Subunidade alfa 3 de Fator de Ligação ao Core/metabolismo , Subunidade alfa 3 de Fator de Ligação ao Core/genética , Camundongos , Fatores de Transcrição/metabolismo , Transcriptoma , Multiômica
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