Spectrum of T ‐lymphocyte activities regulating allergic lung inflammation
Summary
Despite advances in the treatment of asthma, optimization of symptom control remains an unmet need in many patients. These patients, labeled severe asthma, are responsible for a substantial fraction of the disease burden. In these patients, research is needed to define the cellular and molecular pathways contributing to disease which in large part are refractory to corticosteroid treatment. The causes of steroid‐resistant asthma are multifactorial and result from complex interactions of genetics, environmental factors, and innate and adaptive immunity. Adaptive immunity, addressed here, integrates the activities ...
Source: Immunological Reviews - June 28, 2017 Category: Allergy & Immunology Authors: Erwin W. Gelfand, Anthony Joetham, Meiqin Wang, Katsuyuki Takeda, Michaela Schedel Tags: INVITED REVIEW Source Type: research
Mechanisms and treatments for severe, steroid ‐resistant allergic airway disease and asthma
Summary
Severe, steroid‐resistant asthma is clinically and economically important since affected individuals do not respond to mainstay corticosteroid treatments for asthma. Patients with this disease experience more frequent exacerbations of asthma, are more likely to be hospitalized, and have a poorer quality of life. Effective therapies are urgently required, however, their development has been hampered by a lack of understanding of the pathological processes that underpin disease. A major obstacle to understanding the processes that drive severe, steroid‐resistant asthma is that the several endotypes of the disease...
Source: Immunological Reviews - June 28, 2017 Category: Allergy & Immunology Authors: Philip M. Hansbro, Richard Y. Kim, Malcolm R. Starkey, Chantal Donovan, Kamal Dua, Jemma R. Mayall, Gang Liu, Nicole G. Hansbro, Jodie L. Simpson, Lisa G. Wood, Jeremy A. Hirota, Darryl A. Knight, Paul S. Foster, Jay C. Horvat Tags: INVITED REVIEW Source Type: research
Modeling TH2 responses and airway inflammation to understand fundamental mechanisms regulating the pathogenesis of asthma
Summary
In this review, we highlight experiments conducted in our laboratories that have elucidated functional roles for CD4+ T‐helper type‐2 lymphocytes (TH2 cells), their associated cytokines, and eosinophils in the regulation of hallmark features of allergic asthma. Notably, we consider the complexity of type‐2 responses and studies that have explored integrated signaling among classical TH2 cytokines (IL‐4, IL‐5, and IL‐13), which together with CCL11 (eotaxin‐1) regulate critical aspects of eosinophil recruitment, allergic inflammation, and airway hyper‐responsiveness (AHR). Among our most important fin...
Source: Immunological Reviews - June 28, 2017 Category: Allergy & Immunology Authors: Paul S. Foster, Steven Maltby, Helene F. Rosenberg, Hock L. Tay, Simon P. Hogan, Adam M. Collison, Ming Yang, Gerard E. Kaiko, Philip M. Hansbro, Rakesh K. Kumar, Joerg Mattes Tags: INVITED REVIEW Source Type: research
Epigenetic regulation of T ‐helper cell differentiation, memory, and plasticity in allergic asthma
We describe how Th differentiation and plasticity is regulated by epigenetic histone and DNA modifications, with a focus on the regulation of histone methylation by members of the polycomb and trithorax complexes. In addition, we outline environmental influences that could influence epigenetic regulation of Th cells and discuss the potential to regulate Th plasticity and function through drugs targeting the epigenetic machinery. It is also becoming apparent that epigenetic regulation of allergen‐specific memory Th cells may be important in the development and persistence of chronic allergies. Finally, we describe how epi...
Source: Immunological Reviews - June 28, 2017 Category: Allergy & Immunology Authors: Damon J. Tumes, Magdalene Papadopoulos, Yusuke Endo, Atsushi Onodera, Kiyoshi Hirahara, Toshinori Nakayama Tags: INVITED REVIEW Source Type: research
Introduction to “allergic inflammation”
(Source: Immunological Reviews)
Source: Immunological Reviews - June 28, 2017 Category: Allergy & Immunology Authors: Toshinori Nakayama Tags: INTRODUCTION Source Type: research
Issue Information
(Source: Immunological Reviews)
Source: Immunological Reviews - April 30, 2017 Category: Allergy & Immunology Tags: Issue Information Source Type: research
The many ways tissue phagocytes respond to dying cells
Summary
Apoptosis is an important component of normal tissue physiology, and the prompt removal of apoptotic cells is equally essential to avoid the undesirable consequences of their accumulation and disintegration. Professional phagocytes are highly specialized for engulfing apoptotic cells. The recent ability to track cells that have undergone apoptosis in situ has revealed a division of labor among the tissue resident phagocytes that sample them. Macrophages are uniquely programmed to process internalized apoptotic cell‐derived fatty acids, cholesterol and nucleotides, as a reflection of their dominant role in clearin...
Source: Immunological Reviews - April 30, 2017 Category: Allergy & Immunology Authors: J. Magarian Blander Tags: INVITED REVIEW Source Type: research
Ferroptosis: bug or feature?
Summary
Ferroptosis is an iron‐dependent, oxidative form of non‐apoptotic cell death. This form of cell death does not share morphological, biochemical, or genetic similarities with classic necrosis, necroptosis, parthanatos, or other forms of non‐apoptotic cell death. Ferroptosis can be triggered by depleting the cell of the amino acid cysteine, or by inhibiting the phospholipid hydroperoxidase glutathione peroxidase 4 (GPX4). Why certain stimuli trigger ferroptosis instead of another form of cell death, and whether this process could be adaptive in vivo, are two major unanswered questions concerning this process. E...
Source: Immunological Reviews - April 30, 2017 Category: Allergy & Immunology Authors: Scott J. Dixon Tags: INVITED REVIEW Source Type: research
The in vivo evidence for regulated necrosis
Conclusions based on such work might not necessarily be transferrable to disease states in which synchronized, non‐cell autonomous effects occur. Here, we summarize the current knowledge of the pathophysiological relevance of necroptosis in vivo, and in light of this understanding, we reassess the morphological classification of necrosis that is generally used by pathologists. Along these lines, we discuss the paucity of data implicating necroptosis in human disease. Finally, the in vivo relevance of non‐necroptotic forms of necrosis, such as ferroptosis, is addressed. (Source: Immunological Reviews)
Source: Immunological Reviews - April 30, 2017 Category: Allergy & Immunology Authors: Wulf Tonnus, Andreas Linkermann Tags: INVITED REVIEW Source Type: research
The interplay of IKK, NF ‐κB and RIPK1 signaling in the regulation of cell death, tissue homeostasis and inflammation
Summary
Regulated cell death pathways have important functions in host defense and tissue homeostasis. Studies in genetic mouse models provided evidence that cell death could cause inflammation in different tissues. Inhibition of RIPK3‐MLKL‐dependent necroptosis by FADD and caspase‐8 was identified as a key mechanism preventing inflammation in epithelial barriers. Moreover, the interplay between IKK/NF‐κB and RIPK1 signaling was recognized as a critical determinant of tissue homeostasis and inflammation. NEMO was shown to regulate RIPK1 kinase activity‐mediated apoptosis by NF‐κB‐dependent and –independen...
Source: Immunological Reviews - April 30, 2017 Category: Allergy & Immunology Authors: Vangelis Kondylis, Snehlata Kumari, Katerina Vlantis, Manolis Pasparakis Tags: INVITED REVIEW Source Type: research
RIPK3 in cell death and inflammation: the good, the bad, and the ugly
Summary
Necroptosis is a form of cell death that can be observed downstream of death receptor or pattern recognition receptor signaling under certain cellular contexts, or in response to some viral and bacterial infections. The receptor interacting protein kinases‐1 (RIPK1) and RIPK3 are at the core of necroptotic signaling, among other proteins. Because this pathway is normally halted by the pro‐apoptotic protease caspase‐8 and the IAP ubiquitin ligases, how and when necroptosis is triggered in physiological settings are ongoing questions. Interestingly, accumulating evidence suggests that RIPK3 has functions beyond...
Source: Immunological Reviews - April 30, 2017 Category: Allergy & Immunology Authors: Susana Orozco, Andrew Oberst Tags: INVITED REVIEW Source Type: research
RIPK3 ‐driven cell death during virus infections
Abstract
The programmed self‐destruction of infected cells is a powerful antimicrobial strategy in metazoans. For decades, apoptosis represented the dominant mechanism by which the virus‐infected cell was thought to undergo programmed cell death. More recently, however, new mechanisms of cell death have been described that are also key to host defense. One such mechanism in vertebrates is programmed necrosis, or “necroptosis”, driven by receptor‐interacting protein kinase 3 (RIPK3). Once activated by innate immune stimuli, including virus infections, RIPK3 phosphorylates the mixed lineage kinase domain‐like pro...
Source: Immunological Reviews - April 30, 2017 Category: Allergy & Immunology Authors: Jason W. Upton, Maria Shubina, Siddharth Balachandran Tags: INVITED REVIEW Source Type: research
Caspase ‐8: regulating life and death
Summary
Roles for cell death in development, homeostasis, and the control of infections and cancer have long been recognized. Although excessive cell damage results in passive necrosis, cells can be triggered to engage molecular programs that result in cell death. Such triggers include cellular stress, oncogenic signals that engage tumor suppressor mechanisms, pathogen insults, and immune mechanisms. The best‐known forms of programmed cell death are apoptosis and a recently recognized regulated necrosis termed necroptosis. Of the two best understood pathways of apoptosis, the extrinsic and intrinsic (mitochondrial) pathw...
Source: Immunological Reviews - April 30, 2017 Category: Allergy & Immunology Authors: Bart Tummers, Douglas R. Green Tags: INVITED REVIEW Source Type: research
Molecular mechanisms and functions of pyroptosis, inflammatory caspases and inflammasomes in infectious diseases
Summary
Cell death is a fundamental biological phenomenon that is essential for the survival and development of an organism. Emerging evidence also indicates that cell death contributes to immune defense against infectious diseases. Pyroptosis is a form of inflammatory programmed cell death pathway activated by human and mouse caspase‐1, human caspase‐4 and caspase‐5, or mouse caspase‐11. These inflammatory caspases are used by the host to control bacterial, viral, fungal, or protozoan pathogens. Pyroptosis requires cleavage and activation of the pore‐forming effector protein gasdermin D by inflammatory caspases....
Source: Immunological Reviews - April 30, 2017 Category: Allergy & Immunology Authors: Si Ming Man, Rajendra Karki, Thirumala ‐Devi Kanneganti Tags: INVITED REVIEW Source Type: research
Restimulation ‐induced cell death: new medical and research perspectives
Summary
In the periphery, homeostasis of the immune system depends on the equilibrium of expanding and contracting T lymphocytes during immune response. An important mechanism of lymphocyte contraction is clonal depletion of activated T cells by cytokine withdrawal induced death (CWID) and TCR restimulation induced cell death (RICD). Deficiencies in signaling components for CWID and RICD leads to autoimmunune lymphoproliferative disorders in mouse and human. The most important feature of CWID and RICD is clonal specificity, which lends great appeal as a strategy for targeted tolerance induction and treatment of autoimmune ...
Source: Immunological Reviews - April 30, 2017 Category: Allergy & Immunology Authors: Lixin Zheng, Jian Li, Michael Lenardo Tags: INVITED REVIEW Source Type: research
