Interleukin ‐33 (IL‐33): A nuclear cytokine from the IL‐1 family
Summary
Interleukin‐33 (IL‐33) is a tissue‐derived nuclear cytokine from the IL‐1 family abundantly expressed in endothelial cells, epithelial cells and fibroblast‐like cells, both during homeostasis and inflammation. It functions as an alarm signal (alarmin) released upon cell injury or tissue damage to alert immune cells expressing the ST2 receptor (IL‐1RL1). The major targets of IL‐33 in vivo are tissue‐resident immune cells such as mast cells, group 2 innate lymphoid cells (ILC2s) and regulatory T cells (Tregs). Other cellular targets include T helper 2 (Th2) cells, eosinophils, basophils, dendritic cel...
Source: Immunological Reviews - December 16, 2017 Category: Allergy & Immunology Authors: Corinne Cayrol, Jean ‐Philippe Girard Tags: INVITED REVIEW Source Type: research
Interleukin ‐18: Biological properties and role in disease pathogenesis
Summary
Initially described as an interferon (IFN)γ‐inducing factor, interleukin (IL)‐18 is indeed involved in Th1 and NK cell activation, but also in Th2, IL‐17‐producing γδ T cells and macrophage activation. IL‐18, a member of the IL‐1 family, is similar to IL‐1β for being processed by caspase 1 to an 18 kDa‐biologically active mature form. IL‐18 binds to its specific receptor (IL‐18Rα, also known as IL‐1R7) forming a low affinity ligand chain. This is followed by recruitment of the IL‐18Rβ chain. IL‐18 then uses the same signaling pathway as IL‐1 to activate NF‐kB and induce inflamma...
Source: Immunological Reviews - December 16, 2017 Category: Allergy & Immunology Authors: Gilles Kaplanski Tags: INVITED REVIEW Source Type: research
Function and regulation of IL ‐1α in inflammatory diseases and cancer
Summary
The interleukin (IL)‐1 family of cytokines is currently comprised of 11 members that have pleiotropic functions in inflammation and cancer. IL‐1α and IL‐1β were the first members of the IL‐1 family to be described, and both signal via the same receptor, IL‐1R. Over the last decade, much progress has been made in our understanding of biogenesis of IL‐1β and its functions in human diseases. Studies from our laboratory and others have highlighted the critical role of nod‐like receptors (NLRs) and multi‐protein complexes known as inflammasomes in the regulation of IL‐1β maturation. Recent studies ...
Source: Immunological Reviews - December 16, 2017 Category: Allergy & Immunology Authors: Ankit Malik, Thirumala ‐Devi Kanneganti Tags: INVITED REVIEW Source Type: research
The NLRC4 Inflammasome
Summary
15 years ago, the fundamental biology of an inflammatory signaling complex eventually dubbed “the inflammasome” began to unravel in chronologic parallel with the discovery that many inflammatory diseases were associated with its hyperactivity. Though the genetic origins of Familial Mediterranean Fever (FMF, caused my mutations in MEFV) were discovered first, it would take nearly two decades before the mechanistic connections to a PYRIN inflammasome were made. In the interim, the intensive study of the NLRP3 inflammasome, and the diseases associated with its hyperactivation, have largely dictated the paradigm o...
Source: Immunological Reviews - December 16, 2017 Category: Allergy & Immunology Authors: Joseph A. Duncan, Scott W. Canna Tags: INVITED REVIEW Source Type: research
The AIM2 inflammasome: Sensor of pathogens and cellular perturbations
Summary
Recognition of pathogens and altered self must be efficient and highly specific to orchestrate appropriate responses while limiting excessive inflammation and autoimmune reaction to normal self. AIM2 is a member of innate immune sensors that detects the presence of DNA, arguably the most conserved molecules in living organisms. However, AIM2 achieves specificity by detecting altered or mislocalized DNA molecules. It can detect damaged DNA, and the aberrant presence of DNA within the cytosolic compartment such as genomic DNA released into the cytosol upon loss of nuclear envelope integrity. AIM2 is also a key sensor...
Source: Immunological Reviews - December 16, 2017 Category: Allergy & Immunology Authors: J érôme Lugrin, Fabio Martinon Tags: INVITED REVIEW Source Type: research
Metabolic regulation of NLRP3
Summary
A shift in our understanding of macrophage biology has come about as a result of recent discoveries in the area of metabolic reprogramming of macrophages. The NLRP3 inflammasome drives the activation of caspase‐1, leading to the production of IL‐1β, IL‐18, and a type of cell death termed pyroptosis. The NLRP3 inflammasome has been shown to sense metabolites such as palmitate, uric acid, and cholesterol crystals and is inhibited by ketone bodies produced during metabolic flux. The NLRP3 inflammasome has also been shown to be regulated by mitochondrial reactive oxygen species and components of glycolysis, such...
Source: Immunological Reviews - December 16, 2017 Category: Allergy & Immunology Authors: Mark M. Hughes, Luke A.J. O'Neill Tags: INVITED REVIEW Source Type: research
The intra ‐ and extracellular functions of ASC specks
Summary
Inflammasomes are the central signaling hubs of the inflammatory response. They process cytosolic evidence of infection, cell damage, or metabolic disturbances, and elicit a pro‐inflammatory response mediated by members of the interleukin‐1 family of cytokines and pyroptotoic cell death. On the molecular level, this is accomplished by the sensor‐nucleated recruitment and oligomerization of the adapter protein ASC. Once a tunable threshold is reached, cooperative assembly of ASC into linear filaments and their condensation into macromolecular ASC specks promotes an all‐or‐none response. These structures ar...
Source: Immunological Reviews - December 16, 2017 Category: Allergy & Immunology Authors: Bernardo S Franklin, Eicke Latz, Florian Ingo Schmidt Tags: INVITED REVIEW Source Type: research
Autophagy limits activation of the inflammasomes
Summary
Inflammasomes are multiprotein complexes that control the maturation and production of interleukin‐1 family members and play crucial roles in host defense against pathogens. However, dysregulated activation of inflammasomes is associated with intense inflammation, leading to the development of inflammatory diseases. Therefore, inflammasomes must be activated at a proper strength to protect against infection and avoid tissue damage. Recent studies have highlighted the cross‐talk between inflammasome activation and autophagy, the cellular machinery associated with the degradation of intracellular components and m...
Source: Immunological Reviews - December 16, 2017 Category: Allergy & Immunology Authors: Michihiro Takahama, Shizuo Akira, Tatsuya Saitoh Tags: INVITED REVIEW Source Type: research
IL ‐1 and IL‐1 regulatory pathways in cancer progression and therapy
Summary
Inflammation is an important component of the tumor microenvironment. IL‐1 is an inflammatory cytokine which plays a key role in carcinogenesis and tumor progression. IL‐1 is subject to regulation by components of the IL‐1 and IL‐1 receptor (ILR) families. Negative regulators include a decoy receptor (IL‐1R2), receptor antagonists (IL‐1Ra), IL‐1R8, and anti‐inflammatory IL‐37. IL‐1 acts at different levels in tumor initiation and progression, including driving chronic non‐resolving inflammation, tumor angiogenesis, activation of the IL‐17 pathway, induction of myeloid‐derived suppressor ce...
Source: Immunological Reviews - December 16, 2017 Category: Allergy & Immunology Authors: Alberto Mantovani, Isabella Barajon, Cecilia Garlanda Tags: INVITED REVIEW Source Type: research
Interleukin 1 gene polymorphism and susceptibility to disease
Summary
The Interleukin 1 (IL‐1) family plays a central role in the generation and regulation of inflammatory responses, in both innate and adaptive immunity. Although the IL‐1 molecules are traditionally considered to be classical proinflammatory cytokines, their functions are not restricted to inflammation, and they have also been shown to play a key role in a wide range of additional physiological and pathological functions, including learning modulation, sleep, pregnancy, depression, appetite, hematopoiesis, metabolism, and many others. Since their effect as cytokines and regulators of inflammation is so pleiotropi...
Source: Immunological Reviews - December 16, 2017 Category: Allergy & Immunology Authors: Khaled Khazim, Etti Ester Azulay, Batya Kristal, Idan Cohen Tags: INVITED REVIEW Source Type: research
The role of the interleukin ‐1 family in trained immunity
Summary
Immunological memory was long considered a trait exclusive to cells of the adaptive immune system. However, recent studies have shown that after activation of the innate immune system, innate immune cells may undergo long‐term functional reprogramming characterized by the ability to mount either a stronger or attenuated inflammatory response upon reactivation. This phenomenon, which has been termed trained immunity and is a de facto innate immune memory, is regulated by a network of integrated metabolic and epigenetic rewiring. The endogenous mediators that modulate trained immunity in the host are only partially...
Source: Immunological Reviews - December 16, 2017 Category: Allergy & Immunology Authors: Simone J.C.F.M. Moorlag, Rutger Jan R öring, Leo A.B. Joosten, Mihai G. Netea Tags: INVITED REVIEW Source Type: research
Overview of the IL ‐1 family in innate inflammation and acquired immunity
Summary
The interleukin‐1 (IL‐1) family of cytokines and receptors is unique in immunology because the IL‐1 family and Toll‐like receptor (TLR) families share similar functions. More than any other cytokine family, the IL‐1 family is primarily associated with innate immunity. More than 95% of living organisms use innate immune mechanisms for survival whereas less than 5% depend on T‐ and B‐cell functions. Innate immunity is manifested by inflammation, which can function as a mechanism of host defense but when uncontrolled is detrimental to survival. Each member of the IL‐1 receptor and TLR family contains t...
Source: Immunological Reviews - December 16, 2017 Category: Allergy & Immunology Authors: Charles A. Dinarello Tags: INVITED REVIEW Source Type: research
Introduction to the interleukin ‐1 family of cytokines and receptors: Drivers of innate inflammation and acquired immunity
(Source: Immunological Reviews)
Source: Immunological Reviews - December 16, 2017 Category: Allergy & Immunology Authors: Charles A. Dinarello Tags: INTRODUCTION Source Type: research
Issue Information
(Source: Immunological Reviews)
Source: Immunological Reviews - October 13, 2017 Category: Allergy & Immunology Tags: ISSUE INFORMATION Source Type: research
Abscopal, immunological effects of radiotherapy: Narrowing the gap between clinical and preclinical experiences
Summary
Radiotherapy—despite being a local therapy that meanwhile is characterized by an impressively high degree of spatial accuracy—can stimulate systemic phenomena which occasionally lead to regression and rejection of non‐irradiated, distant tumor lesions. These abscopal effects of local irradiation have been observed in sporadic clinical case reports since the beginning of the 20th century, and extensive preclinical work has contributed to identify systemic anti‐tumor immune responses as the underlying driving forces. Although abscopal tumor regression still remains a rare event in the radiotherapeutic routine...
Source: Immunological Reviews - October 13, 2017 Category: Allergy & Immunology Authors: Nikko Brix, Anna Tiefenthaller, Heike Anders, Claus Belka, Kirsten Lauber Tags: INVITED REVIEW Source Type: research
