scholarly journals IL-33 genetics and epigenetics in immune-related diseases

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Eleonora Di Salvo ◽  
Marco Casciaro ◽  
Sebastiano Gangemi
Keyword(s):  
Secretory Pathway ◽  
Interleukin 1 ◽  
Lymphoid Cells ◽  
Th2 Cells ◽  
Interleukin 33 ◽  
Immune Genes ◽  
Helminthic Infections ◽  
Type 2 Immune Response ◽  
Group 2 ◽  
Diverse Data

AbstractInterleukin-33 (IL-33) is a 30KDa protein, which belongs to the Interleukin-1 cytokine family. It is a crucial regulator of innate and adaptive immune responses. This interleukin is additionally involved in the inflammatory reaction versus helminthic infections. Interleukin 33 acts on group 2 innate lymphoid cells and mast cells macrophages, dendritic cells and CD4 + Th2 cells eliciting a type 2 immune response. Moreover, the cytokine can activate the ST2 of Tregs, demonstrating its ability to downregulate inflammation. IL-33 has also an intracellular function by regulating transcription. The active IL-33 doesn’t have a signal peptide, so it’s not released across a normal secretory pathway; the interleukin is released when the cells are damages and acts like an “alarmin”. Its influence on immune activation could be slightly adjusted via fine epigenetic interactions involving cascade pathways and immune genes. Due to the diverse data emerged from different experimental research, we decided span literature to clarify, as much as possible, how IL-33 is influenced by and influence gene expression. The authors reported how its balance is influenced, according to the tissue considered. Fundamental for immune-related diseases, IL-33 has a key role in controlling inflammation. The understanding of the cytokine switch will be fundamental in a near future in order to block or activate some immune pathways. In fact, we could control interleukins effects not only by monoclonal antibodies but also by using siRNA or miRNAs for silencing or expressing key genes.

scholarly journals Interleukin-33 and thymic stromal lymphopoietin, but not interleukin-25, are crucial for development of airway eosinophilia induced by chitin

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ken Arae ◽  
Masashi Ikutani ◽  
Kotaro Horiguchi ◽  
Sachiko Yamaguchi ◽  
Youji Okada ◽  
...  
Keyword(s):  
Allergic Diseases ◽  
Lymphoid Cells ◽  
House Dust Mites ◽  
Atopic Asthma ◽  
Th2 Cells ◽  
Airway Eosinophilia ◽  
Interleukin 33 ◽  
Group 2 ◽  
Underlying Mechanisms ◽  
Mechanisms Of Development

AbstractExposure to various antigens derived from house dust mites (HDM) is considered to be a risk factor for development of certain allergic diseases such as atopic asthma, atopic dermatitis, rhinitis and conjunctivitis. Chitin is an insoluble polysaccharide (β-(1–4)-poly-N-acetyl-d-glucosamine) and a major component in the outer shell of HDMs. Mice exposed to chitin develop asthma-like airway eosinophilia. On the other hand, several lines of evidence show that the effects of chitin on immune responses are highly dependent on the size of chitin particles. In the present study, we show that chitin induced production of IL-33 and TSLP by alveolar and bronchial epithelial cells, respectively, in mice. IL-25, IL-33 and TSLP were reported to be important for group 2 innate lymphoid cell (ILC2)-, but not Th2 cell-, dependent airway eosinophilia in a certain model using chitin beads. Here, we show that—in our murine models—epithelial cell-derived IL-33 and TSLP, but not IL-25, were crucial for activation of resident lung Th2 cells as well as group 2 innate lymphoid cells (ILC2s) to produce IL-5, resulting in development of chitin-induced airway eosinophilia. Our findings provide further insight into the underlying mechanisms of development of HDM-mediated allergic disorders.

scholarly journals The essential function of IL-33 in metabolic regulation

2020 ◽  
Vol 52 (7) ◽  
pp. 768-775 ◽  
Author(s):  
Wenping Li ◽  
Yiyuan Li ◽  
Jin Jin
Keyword(s):  
Metabolic Regulation ◽  
Underlying Mechanism ◽  
Lymphoid Cells ◽  
Regulatory Function ◽  
Current Evidence ◽  
Metabolic Processes ◽  
Interleukin 33 ◽  
Health And Disease ◽  
Essential Function ◽  
Group 2

Abstract Interleukin-33 (IL-33) is produced by various types of cells under physical or pathological conditions. As a multifunctional partner in health and disease, current evidence reveals that IL-33 also participates in several metabolic processes. IL-33 has been proven to contribute to regulating the activity of ST2+ group 2 innate lymphoid cells and regulatory T cells in adipose, which leads to the shift of insulin sensitivity and glucose clearance in glucose metabolism, thermogenesis, and adipocyte beiging in adipose metabolism. In this review, we briefly summarize the biological characteristics of Il-33 and discuss its regulatory function in glucose and adipose metabolism. By clarifying the underlying mechanism of IL-33, we highlight the crosstalk between immune response and metabolic processes mediated by IL-33.

scholarly journals Mepolizumab in the management of severe eosinophilic asthma in adults: current evidence and practical experience

2016 ◽  
Vol 11 (1) ◽  
pp. 40-45 ◽  
Author(s):  
Gilda Varricchi ◽  
Diego Bagnasco ◽  
Matteo Ferrando ◽  
Francesca Puggioni ◽  
Giovanni Passalacqua ◽  
...  
Keyword(s):  
Practical Experience ◽  
Lymphoid Cells ◽  
Th2 Cells ◽  
Current Evidence ◽  
Blood Leukocytes ◽  
Eosinophilic Asthma ◽  
Gm Csf ◽  
Severe Eosinophilic Asthma ◽  
Nk T Cells ◽  
Group 2

Eosinophils represent approximately 1% of peripheral blood leukocytes in normal donors and their maturation and differentiation in the bone marrow are mainly regulated by interleukin (IL)-5 [Broughton et al. 2015]. IL-5, a cytokine that belongs to the β common-chain family, together with IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF), stimulates also the activation and survival of eosinophils and, to some extent, of basophils. IL-5 binds to a heterodimer receptor composed of the specific subunit IL-5Rα and a common subunit βc shared with IL-3 and GM-CSF. Human eosinophils express approximately a three-fold higher level of IL-5Rα compared with basophils. Major sources of IL-5 are T-helper 2 (Th2) cells, mast cells, CD34+ progenitor cells, invariant natural killer (NK) T-cells, group 2 innate lymphoid cells (ILC2s), and eosinophils themselves. ILC2s control not only eosinophil number but also their circadian cycling through the production of IL-5.

scholarly journals Acetylcholine production by group 2 innate lymphoid cells promotes mucosal immunity to helminths

2021 ◽  
Vol 6 (57) ◽  
pp. eabd0359
Author(s):  
Luke B. Roberts ◽  
Corinna Schnoeller ◽  
Rita Berkachy ◽  
Matthew Darby ◽  
Jamie Pillaye ◽  
...  
Keyword(s):  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Mucosal Barrier ◽  
Nippostrongylus Brasiliensis ◽  
Interleukin 33 ◽  
Group 2 ◽  
Maximal Induction

Innate lymphoid cells (ILCs) are critical mediators of immunological and physiological responses at mucosal barrier sites. Whereas neurotransmitters can stimulate ILCs, the synthesis of small-molecule neurotransmitters by these cells has only recently been appreciated. Group 2 ILCs (ILC2s) are shown here to synthesize and release acetylcholine (ACh) during parasitic nematode infection. The cholinergic phenotype of pulmonary ILC2s was associated with their activation state, could be induced by in vivo exposure to extracts of Alternaria alternata or the alarmin cytokines interleukin-33 (IL-33) and IL-25, and was augmented by IL-2 in vitro. Genetic disruption of ACh synthesis by murine ILC2s resulted in increased parasite burdens, lower numbers of ILC2s, and reduced lung and gut barrier responses to Nippostrongylus brasiliensis infection. These data demonstrate a functional role for ILC2-derived ACh in the expansion of ILC2s for maximal induction of type 2 immunity.

scholarly journals Emerging Roles of Interleukin-33-responsive Kidney Group 2 Innate Lymphoid Cells in Acute Kidney Injury

2020 ◽  
Vol 21 (4) ◽  
pp. 1544
Author(s):  
Wei-Yu Chen ◽  
Lung-Chih Li ◽  
Yi-Hsiu Wu ◽  
Jenq-Lin Yang ◽  
Hong-Tai Tzeng
Keyword(s):  
Acute Kidney Injury ◽  
Immune Cells ◽  
Kidney Injury ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Immune Functions ◽  
Loss Of Function ◽  
Interleukin 33 ◽  
Group 2 ◽  
Preclinical Animal Models

Interleukin (IL)-33, a member of the IL-1 family of cytokines, is involved in innate and adaptive immune responses. IL-33 triggers pleiotropic immune functions in multiple types of immune cells, which express the IL-33 receptor, ST2. Recent studies have revealed the potential applications of IL-33 for treating acute kidney injury in preclinical animal models. However, IL-33 and IL-33-responding immune cells are reported to exhibit both detrimental and beneficial roles. The IL-33-mediated immunomodulatory functions have been investigated using loss-of-function approaches, such as IL33-deficient mice, IL-33 antagonists, or administration of exogenous IL-33 recombinant protein. This review will discuss the key findings on IL-33-mediated activation of kidney resident group 2 innate lymphoid cells (ILC2s) and summarize the current understanding of the differential functions of endogenous IL-33 and exogenous IL-33 and their potential implications in treating acute kidney injury.

scholarly journals c-Rel Is Required for IL-33-Dependent Activation of ILC2s

2021 ◽  
Vol 12 ◽  
Author(s):  
Aidil Zaini ◽  
Thomas S. Fulford ◽  
Raelene J. Grumont ◽  
Jessica Runting ◽  
Grace Rodrigues ◽  
...  
Keyword(s):  
Lung Inflammation ◽  
Cytokine Production ◽  
Control Point ◽  
Cell Types ◽  
Lymphoid Cells ◽  
Central Control ◽  
Critical Component ◽  
Interleukin 33 ◽  
Group 2 ◽  
And Function

Group 2 innate lymphoid cells (ILC2s) are emerging as important cellular regulators of homeostatic and disease-associated immune processes. The cytokine interleukin-33 (IL-33) promotes ILC2-dependent inflammation and immunity, with IL-33 having been shown to activate NF-κB in a wide variety of cell types. However, it is currently unclear which NF-κB members play an important role in IL-33-dependent ILC2 biology. Here, we identify the NF-κB family member c-Rel as a critical component of the IL-33-dependent activation of ILC2s. Although c-Rel is dispensable for ILC2 development, it is critical for ILC2 function in the lung, with c-Rel-deficient (c-Rel–/–) mice present a significantly reduced response to papain- and IL-33-induced lung inflammation. We also show that the absence of c-Rel reduces the IL-33-dependent expansion of ILC2 precursors and lower levels of IL-5 and IL-13 cytokine production by mature ILC2s in the lung. Together, these results identify the IL-33-c-Rel axis as a central control point of ILC2 activation and function.

scholarly journals IL-33, an Alarmin of the IL-1 Family Involved in Allergic and Non Allergic Inflammation: Focus on the Mechanisms of Regulation of Its Activity

Cells ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 107
Author(s):  
Corinne Cayrol
Keyword(s):  
Interleukin 1 ◽  
Allergic Inflammation ◽  
Proteolytic Processing ◽  
Lymphoid Cells ◽  
Target Cells ◽  
Interleukin 33 ◽  
Promising Therapeutic Target ◽  
St2 Receptor ◽  
Barrier Tissues

Interleukin-33 (IL-33) is a member of the interleukin-1 (IL-1) family that is expressed in the nuclei of endothelial and epithelial cells of barrier tissues, among others. It functions as an alarm signal that is released upon tissue or cellular injury. IL-33 plays a central role in the initiation and amplification of type 2 innate immune responses and allergic inflammation by activating various target cells expressing its ST2 receptor, including mast cells and type 2 innate lymphoid cells. Depending on the tissue environment, IL-33 plays a wide variety of roles in parasitic and viral host defense, tissue repair and homeostasis. IL-33 has evolved a variety of sophisticated regulatory mechanisms to control its activity, including nuclear sequestration and proteolytic processing. It is involved in many diseases, including allergic, inflammatory and infectious diseases, and is a promising therapeutic target for the treatment of severe asthma. In this review, I will summarize the literature around this fascinating pleiotropic cytokine. In the first part, I will describe the basics of IL-33, from the discovery of interleukin-33 to its function, including its expression, release and signaling pathway. The second part will be devoted to the regulation of IL-33 protein leading to its activation or inactivation.

scholarly journals Interleukin-1 Family Cytokines in Liver Diseases

2015 ◽  
Vol 2015 ◽  
pp. 1-19 ◽  
Author(s):  
Hiroko Tsutsui ◽  
Xianbin Cai ◽  
Shuhei Hayashi
Keyword(s):  
Liver Diseases ◽  
Inflammatory Diseases ◽  
Interleukin 1 ◽  
Allergic Diseases ◽  
Lymphoid Cells ◽  
Leader Peptide ◽  
Gene Encoding ◽  
Membrane Rupture ◽  
Cell Conversion ◽  
Group 2

The gene encoding IL-1 was sequenced more than 30 years ago, and many related cytokines, such as IL-18, IL-33, IL-36, IL-37, IL-38, IL-1 receptor antagonist (IL-1Ra), and IL-36Ra, have since been identified. IL-1 is a potent proinflammatory cytokine and is involved in various inflammatory diseases. Other IL-1 family ligands are critical for the development of diverse diseases, including inflammatory and allergic diseases. Only IL-1Ra possesses the leader peptide required for secretion from cells, and many ligands require posttranslational processing for activation. Some require inflammasome-mediated processing for activation and release, whereas others serve as alarmins and are released following cell membrane rupture, for example, by pyroptosis or necroptosis. Thus, each ligand has the proper molecular process to exert its own biological functions. In this review, we will give a brief introduction to the IL-1 family cytokines and discuss their pivotal roles in the development of various liver diseases in association with immune responses. For example, an excess of IL-33 causes liver fibrosis in mice via activation and expansion of group 2 innate lymphoid cells to produce type 2 cytokines, resulting in cell conversion into pro-fibrotic M2 macrophages. Finally, we will discuss the importance of IL-1 family cytokine-mediated molecular and cellular networks in the development of acute and chronic liver diseases.

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