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1.
Adv Exp Med Biol ; 1444: 219-235, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38467983

RESUMO

The immune system plays a dual role in human health, functioning both as a protector against pathogens and, at times, as a contributor to disease. This feature emphasizes the importance to uncover the underlying causes of its malfunctions, necessitating an in-depth analysis in both pathological and physiological conditions to better understand the immune system and immune disorders. Recent advances in scientific technology have enabled extensive investigations into gene regulation, a crucial mechanism governing cellular functionality. Studying gene regulatory mechanisms within the immune system is a promising avenue for enhancing our understanding of immune cells and the immune system as a whole. The gene regulatory mechanisms, revealed through various methodologies, and their implications in the field of immunology are discussed in this chapter.


Assuntos
Regulação da Expressão Gênica , Sistema Imunitário , Humanos , Epigenômica/métodos
2.
Artigo em Inglês | MEDLINE | ID: mdl-38478380

RESUMO

Endometriosis is a debilitating gynecological disease defined as the presence of endometrium-like epithelium and/or stroma outside the uterine cavity. The most commonly affected sites are the pelvic peritoneum, ovaries, uterosacral ligaments, and the rectovaginal septum. The aberrant tissue responds to hormonal stimulation, undergoing cyclical growth and shedding similar to appropriately located endometrial tissue in the uterus. Common symptoms of endometriosis are painful periods and ovulation, severe pelvic cramping, heavy bleeding, pain during sex, urination and bowel pain, bleeding, and pain between periods. Numerous theories have been proposed to explain the pathogenesis of endometriosis. Sampson's theory of retrograde menstruation is considered to be the most accepted. This theory assumes that endometriosis occurs due to the retrograde flow of endometrial cells through the fallopian tubes during menstruation. However, it has been shown that this process takes place in 90% of women, while endometriosis is diagnosed in only 10% of them. This means that there must be a mechanism that blocks the immune system from removing endometrial cells and interferes with its function, leading to implantation of the ectopic endometrium and the formation of lesions. In this review, we consider the contribution of components of the Major Histocompatibility Complex (MHC)-I-mediated antigen-processing pathway, such as the ERAP, TAP, LMP, LNPEP, and tapasin, to the susceptibility, onset, and severity of endometriosis. These elements can induce significant changes in MHC-I-bound peptidomes that may influence the response of immune cells to ectopic endometrial cells.


Assuntos
Endometriose , Humanos , Feminino , Endometriose/diagnóstico , Endometriose/etiologia , Endometriose/patologia , Endométrio/metabolismo , Endométrio/patologia , Distúrbios Menstruais/complicações , Distúrbios Menstruais/patologia , Sistema Imunitário/patologia , Dor/complicações , Dor/metabolismo
3.
Front Immunol ; 15: 1346035, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38482009

RESUMO

The influence of gut microbiota on physiological processes is rapidly gaining attention globally. Despite being under-studied, there are available data demonstrating a gut microbiota-gonadal cross-talk, and the importance of this axis in reproduction. This study reviews the impacts of gut microbiota on reproduction. In addition, the possible mechanisms by which gut microbiota modulates male and female reproduction are presented. Databases, including Embase, Google scholar, Pubmed/Medline, Scopus, and Web of Science, were explored using relevant key words. Findings showed that gut microbiota promotes gonadal functions by modulating the circulating levels of steroid sex hormones, insulin sensitivity, immune system, and gonadal microbiota. Gut microbiota also alters ROS generation and the activation of cytokine accumulation. In conclusion, available data demonstrate the existence of a gut microbiota-gonadal axis, and role of this axis on gonadal functions. However, majority of the data were compelling evidences from animal studies with a great dearth of human data. Therefore, human studies validating the reports of experimental studies using animal models are important.


Assuntos
Microbioma Gastrointestinal , Microbiota , Animais , Masculino , Feminino , Humanos , Sistema Imunitário , Reprodução , Citocinas
4.
Int J Mol Sci ; 25(5)2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38473965

RESUMO

The transient receptor potential (TRP) ion channels act as cellular sensors and mediate a plethora of physiological processes, including somatosensation, proliferation, apoptosis, and metabolism. Under specific conditions, certain TRP channels are involved in inflammation and immune responses. Thus, focusing on the role of TRPs in immune system cells may contribute to resolving inflammation. In this review, we discuss the distribution of five subfamilies of mammalian TRP ion channels in immune system cells and how these ion channels function in inflammatory mechanisms. This review provides an overview of the current understanding of TRP ion channels in mediating inflammation and may offer potential avenues for therapeutic intervention.


Assuntos
Canais de Potencial de Receptor Transitório , Animais , Humanos , Canais de Potencial de Receptor Transitório/metabolismo , Sistema Imunitário/metabolismo , Inflamação/metabolismo , Mamíferos/metabolismo
5.
Int J Mol Sci ; 25(5)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38474047

RESUMO

Oropharyngeal squamous cell carcinoma (OPSCC), a subset of head and neck squamous cell carcinoma (HNSCC), involves the palatine tonsils, soft palate, base of tongue, and uvula, with the ability to spread to adjacent subsites. Personalized treatment strategies for Human Papillomavirus-associated squamous cell carcinoma of the oropharynx (HPV+OPSCC) are yet to be established. In this article, we summarise our current understanding of the pathogenesis of HPV+OPSCC, the intrinsic role of the immune system, current ICI clinical trials, and the potential role of small molecule immunotherapy in HPV+OPSCC.


Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Neoplasias Orofaríngeas/patologia , Sistema Imunitário/patologia , Papillomavirus Humano , Imunoterapia , Papillomaviridae
7.
Front Immunol ; 15: 1334006, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38464536

RESUMO

Metabolism and immunity are crucial monitors of the whole-body homeodynamics. All cells require energy to perform their basic functions. One of the most important metabolic skills of the cell is the ability to optimally adapt metabolism according to demand or availability, known as metabolic flexibility. The immune cells, first line of host defense that circulate in the body and migrate between tissues, need to function also in environments in which nutrients are not always available. The resilience of immune cells consists precisely in their high adaptive capacity, a challenge that arises especially in the framework of sustained immune responses. Pubmed and Scopus databases were consulted to construct the extensive background explored in this review, from the Kennedy and Lehninger studies on mitochondrial biochemistry of the 1950s to the most recent findings on immunometabolism. In detail, we first focus on how metabolic reconfiguration influences the action steps of the immune system and modulates immune cell fate and function. Then, we highlighted the evidence for considering mitochondria, besides conventional cellular energy suppliers, as the powerhouses of immunometabolism. Finally, we explored the main immunometabolic hubs in the organism emphasizing in them the reciprocal impact between metabolic and immune components in both physiological and pathological conditions.


Assuntos
Sistema Imunitário , Mitocôndrias , Mitocôndrias/metabolismo , Metabolismo Energético
8.
Harefuah ; 163(3): 164-169, 2024 Mar.
Artigo em Hebraico | MEDLINE | ID: mdl-38506358

RESUMO

INTRODUCTION: A powerful adaptive immune system, which includes cellular (T lymphocytes) and humoral (B lymphocytes) immunity, depends on its ability to recognize and protect against millions of different foreign antigens. It does so through an enormous diverse array of T-cell and B-cell receptors, collectively referred to as the adaptive immune repertoire. Using high-throughput sequencing as next generation sequencing (NGS) led to multiple breakthroughs in the field of molecular medicine. It has increased our ability to characterize the immune repertoire in primary immunodeficiency (PID) and to identify defects in diversification processes among other parameters as well. Human inborn errors of immunity represent a unique genotype-phenotype model that enable the study of critical genes' and proteins' role in disease and health. Recent studies regarding immune repertoire profiling of PID allowed us to better define genotype-phenotype correlations in diseases with wide clinical spectrum, the underlining patho-mechanism causing the specific genetic disease, the common features of similar diseases as well as the unique molecular signature for each genetic disease. Immune repertoire knowledge is an integral part of PID research, and aids in improving diagnosis and designing personalized treatment. Nevertheless, NGS has created some challenges that emphasize the need for technologies such as cloud-based platforms like Kusto, enabling scalable data analysis and the incorporation of artificial intelligence techniques.


Assuntos
Inteligência Artificial , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Linfócitos B , Sistema Imunitário
9.
Proc Natl Acad Sci U S A ; 121(14): e2308374121, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38489380

RESUMO

Ultraviolet radiation (UVR) is primarily recognized for its detrimental effects such as cancerogenesis, skin aging, eye damage, and autoimmune disorders. With exception of ultraviolet B (UVB) requirement in the production of vitamin D3, the positive role of UVR in modulation of homeostasis is underappreciated. Skin exposure to UVR triggers local responses secondary to the induction of chemical, hormonal, immune, and neural signals that are defined by the chromophores and extent of UVR penetration into skin compartments. These responses are not random and are coordinated by the cutaneous neuro-immuno-endocrine system, which counteracts the action of external stressors and accommodates local homeostasis to the changing environment. The UVR induces electrical, chemical, and biological signals to be sent to the brain, endocrine and immune systems, as well as other central organs, which in concert regulate body homeostasis. To achieve its central homeostatic goal, the UVR-induced signals are precisely computed locally with transmission through nerves or humoral signals release into the circulation to activate and/or modulate coordinating central centers or organs. Such modulatory effects will be dependent on UVA and UVB wavelengths. This leads to immunosuppression, the activation of brain and endocrine coordinating centers, and the modification of different organ functions. Therefore, it is imperative to understand the underlying mechanisms of UVR electromagnetic energy penetration deep into the body, with its impact on the brain and internal organs. Photo-neuro-immuno-endocrinology can offer novel therapeutic approaches in addiction and mood disorders; autoimmune, neurodegenerative, and chronic pain-generating disorders; or pathologies involving endocrine, cardiovascular, gastrointestinal, or reproductive systems.


Assuntos
Pele , Raios Ultravioleta , Sistema Imunitário , Encéfalo , Sistemas Neurossecretores
10.
Philos Trans R Soc Lond B Biol Sci ; 379(1901): 20230065, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38497271

RESUMO

The Pacific oyster Crassostrea gigas lives in microbe-rich marine coastal systems subjected to rapid environmental changes. It harbours a diversified and fluctuating microbiota that cohabits with immune cells expressing a diversified immune gene repertoire. In the early stages of oyster development, just after fertilization, the microbiota plays a key role in educating the immune system. Exposure to a rich microbial environment at the larval stage leads to an increase in immune competence throughout the life of the oyster, conferring a better protection against pathogenic infections at later juvenile/adult stages. This beneficial effect, which is intergenerational, is associated with epigenetic remodelling. At juvenile stages, the educated immune system participates in the control of the homeostasis. In particular, the microbiota is fine-tuned by oyster antimicrobial peptides acting through specific and synergistic effects. However, this balance is fragile, as illustrated by the Pacific Oyster Mortality Syndrome, a disease causing mass mortalities in oysters worldwide. In this disease, the weakening of oyster immune defences by OsHV-1 µVar virus induces a dysbiosis leading to fatal sepsis. This review illustrates the continuous interaction between the highly diversified oyster immune system and its dynamic microbiota throughout its life, and the importance of this cross-talk for oyster health. This article is part of the theme issue 'Sculpting the microbiome: how host factors determine and respond to microbial colonization'.


Assuntos
Crassostrea , Animais , Crassostrea/genética , Sistema Imunitário
11.
Front Immunol ; 15: 1252445, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38455039

RESUMO

Immune dysfunction in patients with MM affects both the innate and adaptive immune system. Molecules involved in the immune response pathways are essential to determine the ability of cancer cells to escape from the immune system surveillance. However, few data are available concerning the role of immune checkpoint molecules in predicting the myeloma control and immunological scape as mechanism of disease progression. We retrospectively analyzed the clinical impact of the CD200 genotype (rs1131199 and rs2272022) in 291 patients with newly diagnosed MM. Patients with a CD200 rs1131199 GG genotype showed a median overall survival (OS) significantly lower than those with CC+CG genotype (67.8 months versus 94.4 months respectively; p: 0.022) maintaining significance in the multivariate analysis. This effect was specially detected in patients not receiving an autologous stem cell transplant (auto-SCT) (p < 0.001). In these patients the rs1131199 GG genotype negatively influenced in the mortality not related with the progression of MM (p: 0.02) mainly due to infections events.


Assuntos
Mieloma Múltiplo , Humanos , Sistema Imunitário/metabolismo , Mieloma Múltiplo/genética , Mieloma Múltiplo/terapia , Mieloma Múltiplo/diagnóstico , Prognóstico , Estudos Retrospectivos , Transplante de Células-Tronco
12.
Cell Biochem Funct ; 42(2): e3970, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38456500

RESUMO

There is strong evidence that most individuals in the elderly population are characterized by inflamm-aging which refers to a subtle increase in the systemic pro-inflammatory environment and impaired innate immune activation. Although a variety of distinct factors are associated with the progression of inflamm-aging, emerging research is demonstrating a dynamic relationship between the processes of cellular senescence and inflamm-aging. Cellular senescence is a recognized factor governing organismal aging, and through a characteristic secretome, accumulating senescent cells can induce and augment a pro-inflammatory tissue environment that provides a rationale for immune system-independent activation of inflamm-aging and associated diseases. There is also accumulating evidence that inflamm-aging or its components can directly accelerate the development of senescent cells and ultimately senescent cell burden in tissues in a likely vicious inflammatory loop. The present review is intended to describe the emerging senescence-based molecular etiology of inflamm-aging as well as the dynamic reciprocal interactions between inflamm-aging and cellular senescence. Therapeutic interventions concurrently targeting cellular senescence and inflamm-aging are discussed and limitations as well as research opportunities have been deliberated. An effort has been made to provide a rationale for integrating inflamm-aging with cellular senescence both as an underlying cause and therapeutic target for further studies.


Assuntos
Envelhecimento , Senescência Celular , Inflamação , Humanos , Sistema Imunitário
13.
Auton Neurosci ; 252: 103159, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38428324

RESUMO

In the field of psychiatry, biological markers are rarely, if ever, used in the diagnosis of mental health disorders. Clinicians rely primarily on patient histories and behavioral symptoms to identify specific psychopathologies, which makes diagnosis highly subjective. Moreover, therapies for mental health disorders are aimed specifically at attenuating behavioral manifestations, which overlooks the pathophysiological indices of the disease. This is highly evident in posttraumatic stress disorder (PTSD) where inflammation and immune system perturbations are becoming increasingly described. Further, patients with PTSD possess significantly elevated risks of developing comorbid inflammatory diseases such as autoimmune and cardiovascular diseases, which are likely linked (though not fully proven) to the apparent dysregulation of the immune system after psychological trauma. To date, there is little to no evidence that demonstrates current PTSD therapies are able to reverse the increased risk for psychological trauma-induced inflammatory diseases, which suggests the behavioral and somatic consequences of PTSD may not be tightly coupled. This observation provides an opportunity to explore unique mechanisms outside of the brain that contribute to the long-term pathology of PTSD. Herein, we provide an overview of neuroimmune mechanisms, describe what is known regarding innate and adaptive immunity in PTSD, and suggest new directions that are needed to advance the understanding, diagnosis, and treatment of PTSD moving forward.


Assuntos
Doenças Cardiovasculares , Transtornos de Estresse Pós-Traumáticos , Humanos , Encéfalo , Sistema Imunitário , Inflamação
14.
Front Immunol ; 15: 1331486, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38510244

RESUMO

Rheumatoid arthritis (RA) is a systemic autoimmune disorder characterized by swollen joints, discomfort, stiffness, osteoporosis, and reduced functionality. Genetics, smoking, dust inhalation, high BMI, and hormonal and gut microbiota dysbiosis are all likely causes of the onset or development of RA, but the underlying mechanism remains unknown. Compared to healthy controls, patients with RA have a significantly different composition of gut microbiota. It is well known that the human gut microbiota plays a key role in the initiation, maintenance, and operation of the host immune system. Gut microbiota dysbiosis has local or systematic adverse effects on the host immune system, resulting in host susceptibility to various diseases, including RA. Studies on the intestinal microbiota modulation and immunomodulatory properties of probiotics have been reported, in order to identify their potential possibility in prevention and disease activity control of RA. This review summarized current studies on the role and potential mechanisms of gut microbiota in the development and progression of RA, as well as the preventative and therapeutic effects and potential mechanisms of probiotics on RA. Additionally, we proposed the challenges and difficulties in the application of probiotics in RA, providing the direction for the research and application of probiotics in the prevention of RA.


Assuntos
Artrite Reumatoide , Microbioma Gastrointestinal , Probióticos , Humanos , Disbiose/complicações , Artrite Reumatoide/tratamento farmacológico , Sistema Imunitário , Probióticos/uso terapêutico
15.
Front Immunol ; 15: 1286352, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38515744

RESUMO

The world's largest extant carnivorous marsupial, the Tasmanian devil, is challenged by Devil Facial Tumor Disease (DFTD), a fatal, clonally transmitted cancer. In two decades, DFTD has spread across 95% of the species distributional range. A previous study has shown that factors such as season, geographic location, and infection with DFTD can impact the expression of immune genes in Tasmanian devils. To date, no study has investigated within-individual immune gene expression changes prior to and throughout the course of DFTD infection. To explore possible changes in immune response, we investigated four locations across Tasmania that differed in DFTD exposure history, ranging between 2 and >30 years. Our study demonstrated considerable complexity in the immune responses to DFTD. The same factors (sex, age, season, location and DFTD infection) affected immune gene expression both across and within devils, although seasonal and location specific variations were diminished in DFTD affected devils. We also found that expression of both adaptive and innate immune genes starts to alter early in DFTD infection and continues to change as DFTD progresses. A novel finding was that the lower expression of immune genes MHC-II, NKG2D and CD8 may predict susceptibility to earlier DFTD infection. A case study of a single devil with regressed tumor showed opposite/contrasting immune gene expression patterns compared to the general trends observed across devils with DFTD infection. Our study highlights the complexity of DFTD's interactions with the host immune system and the need for long-term studies to fully understand how DFTD alters the evolutionary trajectory of devil immunity.


Assuntos
Daunorrubicina/análogos & derivados , Neoplasias Faciais , Marsupiais , Animais , Neoplasias Faciais/genética , Neoplasias Faciais/veterinária , Sistema Imunitário/patologia , Expressão Gênica , Marsupiais/genética
16.
Exp Dermatol ; 33(3): e15029, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38429868

RESUMO

Skin is now emerging as a complex realm of three chief systems viz. immune system, nervous system, and endocrine system. The cells involved in their intricate crosstalk, namely native skin cells, intra-cutaneous immune cells and cutaneous sensory neurons have diverse origin and distinct functions. However, recent studies have explored their role beyond their pre-defined functional boundaries, such that the cells shun their traditional functions and adopt unconventional roles. For example, the native skin cells, apart from providing for basic structural framework of skin, also perform special immune functions and participate in extensive neuro-endocrine circuitry, which were traditionally designated as functions of cutaneous resident immune cells and sensory neurons respectively. At the cellular level, this unique collaboration is brought out by special molecules called neuromediators including neurotransmitters, neuropeptides, neurotrophins, neurohormones and cytokines/chemokines. While this intricate crosstalk is essential for maintaining cutaneous homeostasis, its disruption is seen in various cutaneous diseases. Recent study models have led to a paradigm shift in our understanding of pathophysiology of many such disorders. In this review, we have described in detail the interaction of immune cells with neurons and native skin cells, role of neuromediators, the endocrine aspect in skin and current understanding of cutaneous neuro-immuno-endocrine loop in one of the commonest skin diseases, psoriasis. An accurate knowledge of this unique crosstalk can prove crucial in understanding the pathophysiology of different skin diseases and allow for generation of targeted therapeutic modalities.


Assuntos
Neuropeptídeos , Dermatopatias , Humanos , Pele , Sistemas Neurossecretores , Sistema Imunitário/fisiologia , Neurotransmissores
17.
Nature ; 627(8003): 277-279, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38448528
18.
Arch Microbiol ; 206(4): 145, 2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38461447

RESUMO

According to recent research, bacterial imbalance in the gut microbiota and breast tissue may be linked to breast cancer. It has been discovered that alterations in the makeup and function of different types of bacteria found in the breast and gut may contribute to growth and advancement of breast cancer in several ways. The main role of gut microbiota is to control the metabolism of steroid hormones, such as estrogen, which are important in raising the risk of breast cancer, especially in women going through menopause. On the other hand, because the microbiota can influence mucosal and systemic immune responses, they are linked to the mutual interactions between cancer cells and their local environment in the breast and the gut. In this regard, the current review thoroughly explains the mode of action of probiotics and microbiota to eradicate the malignancy. Furthermore, immunomodulation by microbiota and probiotics is described with pathways of their activity.


Assuntos
Neoplasias da Mama , Microbiota , Probióticos , Feminino , Humanos , Prebióticos , Neoplasias da Mama/prevenção & controle , Sistema Imunitário , Inflamação , Hormônios
19.
Proc Biol Sci ; 291(2016): 20232036, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38320611

RESUMO

Early life microbial colonizers shape and support the immature vertebrate immune system. Microbial colonization relies on the vertical route via parental provisioning and the horizontal route via environmental contribution. Vertical transmission is mostly a maternal trait making it hard to determine the source of microbial colonization in order to gain insight into the establishment of the microbial community during crucial development stages. The evolution of unique male pregnancy in pipefishes and seahorses enables the disentanglement of both horizontal and vertical transmission, but also facilitates the differentiation of maternal versus paternal provisioning ranging from egg development, to male pregnancy and early juvenile development. Using 16S rRNA amplicon sequencing and source-tracker analyses, we revealed how the distinct origins of transmission (maternal, paternal and horizontal) shaped the juvenile internal and external microbiome establishment in the broad-nosed pipefish Syngnathus typhle. Our data suggest that transovarial maternal microbial contribution influences the establishment of the juvenile gut microbiome whereas paternal provisioning mainly shapes the juvenile external microbiome. The identification of juvenile key microbes reveals crucial temporal shifts in microbial development and enhances our understanding of microbial transmission routes, colonization dynamics and their impact on lifestyle evolution.


Assuntos
Microbioma Gastrointestinal , Microbiota , Smegmamorpha , Animais , Masculino , RNA Ribossômico 16S/genética , Sistema Imunitário , Smegmamorpha/genética
20.
Nat Immunol ; 25(3): 405-417, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38413722

RESUMO

The immune system comprises diverse specialized cell types that cooperate to defend the host against a wide range of pathogenic threats. Recent advancements in single-cell and spatial multi-omics technologies provide rich information about the molecular state of immune cells. Here, we review how the integration of single-cell and spatial multi-omics data with prior knowledge-gathered from decades of detailed biochemical studies-allows us to obtain functional insights, focusing on gene regulatory processes and cell-cell interactions. We present diverse applications in immunology and critically assess underlying assumptions and limitations. Finally, we offer a perspective on the ongoing technological and algorithmic developments that promise to get us closer to a systemic mechanistic understanding of the immune system.


Assuntos
Sistema Imunitário , Multiômica , Comunicação Celular
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