scholarly journals The cGAS-STING Pathway: A Promising Immunotherapy Target

2021 ◽  
Vol 12 ◽  
Author(s):  
Liang Ou ◽  
Ao Zhang ◽  
Yuxing Cheng ◽  
Ying Chen
Keyword(s):  
Innate Immunity ◽  
T Lymphocytes ◽  
Immune Responses ◽  
Adaptive Immunity ◽  
Inflammatory Diseases ◽  
Macrophage Polarization ◽  
Signal Pathway ◽  
Autoimmune And Inflammatory Diseases ◽  
Immunotherapy Target ◽  
Sting Pathway

With the continuous development of immunotherapy, researchers have paid more attention to the specific immune regulatory mechanisms of various immune responses in different diseases. As a novel and vital innate immune signal pathway, the cGAS-STING signal pathway activated by nucleic acid substances, interplays with other immune responses, by which it participates in regulating cancer, autoimmune and inflammatory diseases, microbial and parasitic infectious diseases, and other diseases. With the exception of its role in innate immunity, the growing list of researches demonstrated expanding roles of the cGAS-STING signal pathway in bridging the innate immunity (macrophage polarization) with the adaptive immunity (T lymphocytes differentiation). Macrophages and T lymphocytes are the most representative cells of innate immunity and adaptive immunity, respectively. Their polarization or differentiation are involved in the pathogenesis and progression of various diseases. Here we mainly summarized recent advanced discoveries of how the cGAS-STING signal pathway regulated macrophages polarization and T lymphocytes differentiation in various diseases and vaccine applications, providing a promising direction for the development and clinical application of immunotherapeutic strategies for related diseases.

scholarly journals Bridging autoinflammatory and autoimmune diseases

2021 ◽  
Vol 33 (1) ◽  
Author(s):  
Emad M. El-Shebiny ◽  
Enas S. Zahran ◽  
Sabry A. Shoeib ◽  
Eman S. Habib
Keyword(s):  
Innate Immunity ◽  
T Lymphocytes ◽  
Autoimmune Diseases ◽  
Adaptive Immunity ◽  
High Titre ◽  
The Other ◽  
Clinical Spectrum ◽  
Autoinflammatory Diseases ◽  
Main Body ◽  
B And T Lymphocytes

Abstract Background Autoimmunity is used to cause by impairment of adaptive immunity alone, whereas autoinflammatory was originally defined as a consequence of unregulated innate immunity. So, the pathogenetic mechanisms of autoimmune diseases were well-thought-out to be mediated by B and T lymphocytes. Whereas, autoinflammatory diseases were defined as unprovoked times of inflammation with the absence of a high titre of autoantibodies. Main body of the abstract Autoimmune and autoinflammatory diseases were split into two groups, but considering the similarities, it can be considered as only one group of diseases with a large immune pathological and clinical spectrum which involves at one end pure autoimmune diseases and the other pure autoinflammatory diseases. Conclusions We can safely conclude that there is bridging between autoinflammatory and autoimmune diseases.

scholarly journals The Interleukins Orchestrate Mucosal Immune Responses to Salmonella Infection in the Intestine

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3492
Author(s):  
Fu-Chen Huang
Keyword(s):  
Innate Immunity ◽  
Immune Responses ◽  
Natural Killer ◽  
Adaptive Immunity ◽  
Alternative Therapy ◽  
Muramyl Dipeptide ◽  
Protective Effects ◽  
Salmonella Infection ◽  
Intestinal Pathogens ◽  
Anti Inflammatory

Salmonella infection remains one of the major public health problems in the world, with increasing resistance to antibiotics. The resolution is to explore the pathogenesis of the infection and search for alternative therapy other than antibiotics. Immune responses to Salmonella infection include innate and adaptive immunity. Flagellin or muramyl dipeptide from Salmonella, recognized by extracellular Toll-like receptors and intracellular nucleotide-binding oligomerization domain2, respectively, induce innate immunity involving intestinal epithelial cells, neutrophils, macrophages, dendric cells and lymphocytes, including natural killer (NK) and natural killer T (NKT) cells. The cytokines, mostly interleukins, produced by the cells involved in innate immunity, stimulate adaptive immunity involving T and B cells. The mucosal epithelium responds to intestinal pathogens through its secretion of inflammatory cytokines, chemokines, and antimicrobial peptides. Chemokines, such as IL-8 and IL-17, recruit neutrophils into the cecal mucosa to defend against the invasion of Salmonella, but induce excessive inflammation contributing to colitis. Some of the interleukins have anti-inflammatory effects, such as IL-10, while others have pro-inflammatory effects, such as IL-1β, IL-12/IL-23, IL-15, IL-18, and IL-22. Furthermore, some interleukins, such as IL-6 and IL-27, exhibit both pro- and anti-inflammatory functions and anti-microbial defenses. The majority of interleukins secreted by macrophages and lymphocytes contributes antimicrobial defense or protective effects, but IL-8 and IL-10 may promote systemic Salmonella infection. In this article, we review the interleukins involved in Salmonella infection in the literature.

scholarly journals PPARγAgonists in Adaptive Immunity: What Do Immune Disorders and Their Models Have to Tell Us?

PPAR Research ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Laurindo Ferreira da Rocha Junior ◽  
Andréa Tavares Dantas ◽  
Ângela Luzia Branco Pinto Duarte ◽  
Moacyr Jesus Barreto de Melo Rego ◽  
Ivan da Rocha Pitta ◽  
...  
Keyword(s):  
Adaptive Immunity ◽  
Inflammatory Diseases ◽  
Cell Lineage ◽  
Adaptive Immune System ◽  
Innate And Adaptive Immunity ◽  
Adaptive Immune ◽  
Cytokines And Chemokines ◽  
Autoimmune And Inflammatory Diseases ◽  
Ppar Agonists ◽  
T Cell Survival

Adaptive immunity has evolved as a very powerful and highly specialized tool of host defense. Its classical protagonists are lymphocytes of the T- and B-cell lineage. Cytokines and chemokines play a key role as effector mechanisms of the adaptive immunity. Some autoimmune and inflammatory diseases are caused by disturbance of the adaptive immune system. Recent advances in understanding the pathogenesis of autoimmune diseases have led to research on new molecular and therapeutic targets. PPARγare members of the nuclear receptor superfamily and are transcription factors involved in lipid metabolism as well as innate and adaptive immunity. PPARγis activated by synthetic and endogenous ligands. Previous studies have shown that PPAR agonists regulate T-cell survival, activation and T helper cell differentiation into effector subsets: Th1, Th2, Th17, and Tregs. PPARγhas also been associated with B cells. The present review addresses these issues by placing PPARγagonists in the context of adaptive immune responses and the relation of the activation of these receptors with the expression of cytokines involved in adaptive immunity.

scholarly journals Intestinal Microbes in Autoimmune and Inflammatory Disease

2020 ◽  
Vol 11 ◽  
Author(s):  
Wan-Jung H. Wu ◽  
Daniel F. Zegarra-Ruiz ◽  
Gretchen E. Diehl
Keyword(s):  
Genetic Variation ◽  
Immune Responses ◽  
Autoimmune Diseases ◽  
Inflammatory Disease ◽  
Inflammatory Diseases ◽  
Current Evidence ◽  
Intestinal Microbes ◽  
Multiple Factors ◽  
Autoimmune And Inflammatory Diseases ◽  
Progression Of Disease

Autoimmune diseases and chronic inflammatory disorders are characterized by dysregulated immune responses resulting in excessive and uncontrolled tissue inflammation. Multiple factors including genetic variation, environmental stimuli, and infection are all thought to contribute to continued inflammation and pathology. Current evidence supports the microbiota as one such factor with emerging data linking commensal organisms to the onset and progression of disease. In this review, we will discuss links between the microbiota and specific diseases as well as highlight common pathways that link intestinal microbes with multiple autoimmune and inflammatory diseases.

Dual-specificity phosphatase 1: a critical regulator of innate immune responses

2006 ◽  
Vol 34 (6) ◽  
pp. 1018-1023 ◽  
Author(s):  
S.M. Abraham ◽  
A.R. Clark
Keyword(s):  
Innate Immunity ◽  
Immune Responses ◽  
P38 Mapk ◽  
Time Course ◽  
Inflammatory Diseases ◽  
Innate Immune ◽  
Mitogen Activated Protein Kinase ◽  
Innate Immune Responses ◽  
Inflammatory Stimuli ◽  
Mitogen Activated Protein

Innate immune responses are critically dependent on MAPK (mitogen-activated protein kinase) signalling pathways, in particular JNK (c-Jun N-terminal kinase) and p38 MAPK. Both of these kinases are negatively regulated via their dephosphorylation by DUSP1 (dual­-specificity phosphatase 1). Several pro- and anti-inflammatory stimuli converge to regulate the DUSP1 gene and to modulate the time course of its expression. In turn, the pattern of expression of DUSP1 dictates the kinetics of activation of JNK and p38 MAPK, and this influences the expression of several mediators of innate immunity. DUSP1 is therefore a central regulator of innate immunity, and its expression can profoundly affect the outcome of inflammatory challenges. We discuss possible implications for immune-mediated inflammatory diseases and their treatment.

scholarly journals The Kynurenine Pathway—New Linkage between Innate and Adaptive Immunity in Autoimmune Endocrinopathies

2021 ◽  
Vol 22 (18) ◽  
pp. 9879
Author(s):  
Anna Krupa ◽  
Irina Kowalska
Keyword(s):  
Immune System ◽  
Adaptive Immunity ◽  
Immune Cells ◽  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Kynurenine Pathway ◽  
Wide Range ◽  
Organ Specific ◽  
Autoimmune And Inflammatory Diseases

The kynurenine pathway (KP) is highly regulated in the immune system, where it promotes immunosuppression in response to infection or inflammation. Indoleamine 2,3-dioxygenase 1 (IDO1), the main enzyme of KP, has a broad spectrum of activity on immune cells regulation, controlling the balance between stimulation and suppression of the immune system at sites of local inflammation, relevant to a wide range of autoimmune and inflammatory diseases. Various autoimmune diseases, among them endocrinopathies, have been identified to date, but despite significant progress in their diagnosis and treatment, they are still associated with significant complications, morbidity, and mortality. The precise cellular and molecular mechanisms leading to the onset and development of autoimmune disease remain poorly clarified so far. In breaking of tolerance, the cells of the innate immunity provide a decisive microenvironment that regulates immune cells’ differentiation, leading to activation of adaptive immunity. The current review provided a comprehensive presentation of the known role of IDO1 and KP activation in the regulation of the innate and adaptive arms of the immune system. Significant attention has been paid to the immunoregulatory role of IDO1 in the most prevalent, organ-specific autoimmune endocrinopathies—type 1 diabetes mellitus (T1DM) and autoimmune thyroiditis.

scholarly journals Effect of Poli I:C in murine model of autoimmune thyroiditis

2015 ◽  
Author(s):  
Carolina Loreto Vera Sepulveda ◽  
MIguel Barria Maldonado
Keyword(s):  
Innate Immunity ◽  
Dendritic Cells ◽  
Autoimmune Diseases ◽  
Murine Model ◽  
Autoimmune Thyroiditis ◽  
Hashimoto’S Thyroiditis ◽  
Inflammatory Diseases ◽  
Hashimoto's Thyroiditis ◽  
Autoimmune And Inflammatory Diseases

Hashimoto's thyroiditis is one of the most common autoimmune diseases in humans and, similar to other autoimmune diseases, is multifactorial in nature. Moreover, the expression of TLRs has been implicated in the pathogenesis of autoimmune and inflammatory diseases, such as diabetes and insulinitis. The TLRs are a family of at least 10 receptors associated with innate immunity that are present in monocytes, macrophages, and dendritic cells, which recognize highly conserved patterns of the surface of microorganisms, such as LPS, peptidoglycan, and dsRNA and CpG sequences.

cGAS-STING-mediated IFN-I response in host defense and neuro-inflammatory diseases

2021 ◽  
Vol 19 ◽  
Author(s):  
Kai Chen ◽  
Chuan Lai ◽  
Yin Su ◽  
Wen Dai Bao ◽  
Liu Nan Yang ◽  
...  
Keyword(s):  
Immune Responses ◽  
Host Defense ◽  
Inflammatory Diseases ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Danger Signal ◽  
Downstream Signaling ◽  
Pathway Activation ◽  
Sting Pathway ◽  
Lateral Sclerosis

: The presence of foreign or misplaced nucleic acids is a danger signal that triggers innate immune responses through activating cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS) and binding to its downstream signaling effector stimulator of interferon genes (STING). Then the cGAS–STING pathway activation links nucleic acid sensing to immune responses and pathogenic entities clearance. However, overactivation of this signaling pathway leads to fatal immune disorders and contributes to the progression of many human inflammatory diseases. Therefore, optimal activation of this pathway is crucial for the elimination of invading pathogens and the maintenance of immune homeostasis. In this review, we will summarize its fundamental roles in initiating host defense against invading pathogens and discuss its pathogenic roles in multiple neuro-inflammatory diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS) and other neurodegenerative diseases.

scholarly journals Schistosome-Derived Molecules as Modulating Actors of the Immune System and Promising Candidates to Treat Autoimmune and Inflammatory Diseases

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Luis Janssen ◽  
Gisele Lorranna Silva Santos ◽  
Herick Sampaio Muller ◽  
Anderson Rodrigues Araújo Vieira ◽  
Tatiana Amabile de Campos ◽  
...  
Keyword(s):  
Immune Responses ◽  
Defense Mechanisms ◽  
Inflammatory Diseases ◽  
Adaptive Responses ◽  
Immunomodulatory Effects ◽  
Larval Stages ◽  
Helminth Infections ◽  
Autoimmune And Inflammatory Diseases ◽  
Potential Applications ◽  
Parasite Infections

It is long known that some parasite infections are able to modulate specific pathways of host’s metabolism and immune responses. This modulation is not only important in order to understand the host-pathogen interactions and to develop treatments against the parasites themselves but also important in the development of treatments against autoimmune and inflammatory diseases. Throughout the life cycle of schistosomes the mammalian hosts are exposed to several biomolecules that are excreted/secreted from the parasite infective stage, named cercariae, from their tegument, present in adult and larval stages, and finally from their eggs. These molecules can induce the activation and modulation of innate and adaptive responses as well as enabling the evasion of the parasite from host defense mechanisms. Immunomodulatory effects of helminth infections and egg molecules are clear, as well as their ability to downregulate proinflammatory cytokines, upregulate anti-inflammatory cytokines, and drive a Th2 type of immune response. We believe that schistosomes can be used as a model to understand the potential applications of helminths and helminth-derived molecules against autoimmune and inflammatory diseases.

scholarly journals cGAS/STING: novel perspectives of the classic pathway

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Menghui Gao ◽  
Yuchen He ◽  
Haosheng Tang ◽  
Xiangyu Chen ◽  
Shuang Liu ◽  
...  
Keyword(s):  
Immune Response ◽  
Inflammatory Diseases ◽  
Er Stress Response ◽  
Autophagy Induction ◽  
Autoimmune And Inflammatory Diseases ◽  
Secretory Phenotype ◽  
New Perspective ◽  
Sting Pathway ◽  
Exciting Area ◽  
Cancerous Cells

Abstract Cyclic GMP-AMP (cGAMP) synthase (cGAS) is a cytosolic DNA sensor and innate immune response initiator. Binding with exogenous or endogenous nucleic acids, cGAS activates its downstream adaptor, stimulator of interferon genes (STING). STING then triggers protective immune to enable the elimination of the pathogens and the clearance of cancerous cells. Apparently, aberrantly activated by self-DNA, cGAS/STING pathway is threatening to cause autoimmune and inflammatory diseases. The effects of cGAS/STING in defenses against infection and autoimmune diseases have been well studied, still it is worthwhile to discuss the roles of cGAS/STING pathway beyond the “classical” realm of innate immunity. Recent studies have revealed its involvement in non-canonical inflammasome formation, calcium hemostasis regulation, endoplasmic reticulum (ER) stress response, perception of leaking mitochondrial DNA (mtDNA), autophagy induction, cellular senescence and senescence-associated secretory phenotype (SASP) production, providing an exciting area for future exploration. Previous studies generally focused on the function of cGAS/STING pathway in cytoplasm and immune response. In this review, we summarize the latest research of this pathway on the regulation of other physiological process and STING independent reactions to DNA in micronuclei and nuclei. Together, these studies provide a new perspective of cGAS/STING pathway in human diseases.

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