International Reviews of Immunology最新文献

Mammalian immune system is a complex amalgam of diverse cellular and noncellular components such as cytokines, receptors and co-receptors. FAM26F (family with sequence similarity 26, member F) is a recently identified tetraspanin-like membrane glycoprotein which is predicted to make homophilic interactions and potential synapses between several immune cells including CD4⁺, CD8⁺, NK, dendritic cells and macrophages. Various whole transcriptome analyses have demonstrated the differential expression of FAM26F in several bacterial, viral and parasitic infections, in certain pathophysiological conditions such as liver and heart transplantation, and in various cancers. The complete understanding of transcriptional regulation of FAM26F is in its infancy however it is up regulated by various stimulants such as polyI:C, LPS, INF gamma and TNF alpha, and via various proposed pathways including TLR3, TLR4 IFN-β and Dectin-1. These pathways can merge in STAT1 activation. The synergistic expression of FAM26F on both NK-cells and myeloid dendritic cells is required to activate NK-cells against tumors via its cytoplasmic tail, thus emphasizing therapeutic potential of FAM26F for NK sensitive tumors. Current review provides a comprehensive basis to propose that FAM26F expression level is at least a hallmark for IFN-γ-lead immune responses and thus can proficiently be regarded as an early diagnostic marker. Future investigation dissecting the role of FAM26F in activation of various immune cell populations in local amplification by cell-cell contact is crucial to provide the missing link imperative for elucidating the relevance of this protein in immune responses.

T cells populate the skin to provide an effective immunosurveillance against external insults and to maintain tissue homeostasis. Most cutaneous T cells are αβ T cells, however, γδ T cells also exist although in much lower frequency. Different subsets of αβ T cells can be found in the skin, such as short-lived effector T cells, central memory T cells, effector memory T cells, and tissue-resident memory T cells. Their differential biology, function, and location provide an ample spectrum of immune responses in the skin. Foxp3+ memory regulatory T cells have a pivotal role in maintaining homeostasis in the skin and their dysregulation has been linked with different skin pathologies. The skin also contains populations of non-classical T cells, such as γδ T cells, NK T cells, and MR1-restricted T cells. Their role in skin homeostasis and response to pathogens has been well established in the past years, however, there is also growing evidence of their role in mediating allergic skin inflammation and promoting sensitization to allergens. In this review, we provide an updated overview on the different subsets of T cells that populate the skin with a specific focus on their role in allergic skin inflammation.

Cardiovascular disease is the most common cause of death, which has the highest mortality rate worldwide. Although a diverse range of inflammatory diseases can affect the cardiovascular system, however, heart failure and stroke occur due to atherosclerosis. Atherosclerosis is a chronic autoinflammatory disease of small to large vessels in which different immune mediators are involved in lipid plaque formation and inflammatory vascular remodeling process. A better understanding of the pathophysiology of atherosclerosis may lead to uncovering immunomodulatory therapies. Despite present diagnostic and therapeutic methods, the lack of immunotherapy in the prevention and treatment of atherosclerosis is perceptible. In this review, we will discuss the promising immunological-based therapeutics and novel preventive approaches for atherosclerosis. This study could provide new insights into a better perception of targeted therapeutic pathways and biological therapies. [Formula: see text].

As a natural function, antibodies defend the host from infected cells and pathogens by recognizing their pathogenic determinants. Antibodies (Abs) gained wide acceptance with an enormous impact on human health and have predominantly captured the arena of bio-therapeutics and bio-diagnostics. The scope of Ab-based biologics is vast, and it is likely to solve many unmet clinical needs in future. The majority of attention is now devoted to developing innovative technologies for manufacturing and engineering Abs, better suited to satisfy human needs. The advent of Ab engineering technologies (AET) led to phenomenal developments leading to the generation of Abs-/Ab-derived molecules with desirable functional properties proportional to their expanding requirements. Evolution brought by AET, from the naturally occurring Ab forms to several advanced Ab formats and derivatives, was much needed as it is of great interest to the pharmaceutical industry. Thus, numerous advancements in AET have propelled success in therapeutic Ab development, along with the potential for ever-increasing improvements. Unique characteristics of Abs, such as its diversity, specificity, structural integrity and an array of possible applications, together inspire continuous innovation in the field. Overall, the AET could assist in conquer of several limitations of Abs in terms of their applicability in the field of therapeutics, diagnostics and research; AET has so far led to the production of next-generation Abs, which have revolutionized these arenas. Here in this review, we discuss the various distinguished engineering platforms for Ab development and the progress in modern therapeutics by the so-called "next-generation Abs."

Inflammation plays indispensable roles in building the immune responses such as acquired immunity against harmful pathogens. Furthermore, it is essential for maintaining biological homeostasis in ever-changing conditions. Pattern-recognition receptors (PRRs) reside in cell membranes, endosomes or cytoplasm, and function as triggers for inflammatory responses. Binding of pathogen- or self-derived components, such as DNA, to PRRs activates downstream signaling cascades, resulting in the production of a series of pro-inflammatory cytokines and type I interferons (IFNs). While these series of responses are essential for host defense, the unexpected release of DNA from the nucleus or mitochondria of host cells can lead to autoimmune and autoinflammatory diseases. In this review, we focus on DNA-sensing mechanisms via PRRs and the disorders and extraordinary conditions caused by self-derived DNA.

Metabolic reprogramming is a hallmark of solid cancers. Macrophages as major constituents of immune system take important roles in regulation of tumorigenesis. Pro-tumor M2 macrophages preferentially use oxidative phosphorylation (OXPHOS) to meet their metabolic demands, while anti-tumor M1 macrophages use glycolysis as their dominant metabolic source. Dysregulation in metabolic systems is a driving force of skewing macrophages from M1 toward M2 phenotypical state. Hyperactive M1 macrophages, for instance, release metabolic products that are contributed to M2 macrophage polarization. Thus, metabolic remodeling through reinstating normalization in metabolic systems can be an effective tool in cancer therapy. The key focus of this review is over metabolic systems in macrophages and factors influencing their metabolic acquisition and reprogramming in cancer, as well as discussing bout strategies to adjust macrophage metabolism and reeducation toward M1-like phenotype.

The innate lymphoid cell (ILC) system comprising of the circulating and tissue-resident cells is known to clear infectious pathogens, establish immune homeostasis as well as confer antitumor immunity. Human natural killer cells (hNKs) and other ILCs carry out mopping of the infectious pathogens and perform cytolytic activity regulated by the non-adaptive immune system. The NK cells generate immunological memory and rapid recall response tightly regulated by the adaptive immunity. The interaction of NK and B cell, and its role to induce the pathogen specific immunity is not fully understood. Hence, present article sheds light on the interaction between NK and B cells and resulting immune responses in the infectious diseases. The immune responses elicited by the NK-B cell interaction is of particular importance for developing therapeutic vaccines against the infectious pathogens. Further, experimental evidences suggest the immune-response driven by NK cell population elicits the host-specific antibodies and memory B cells. Also, recently developed humanized immune system (HIS) mice and their importance in to understanding the NK-B cell interaction and resulting pathogen specific immunity has been discussed.

Ferroptosis is a type of non-apoptotic cell death, which demonstrates a definite iron-dependent expression pattern and is associated with lipid peroxidation. Glutathione peroxidase 4 (GPX4) is a key regulator of ferroptosis. Ferroptosis is involved in the development and progression of various diseases, such as cancer, tissue ischemia-reperfusion injury, neurological diseases, and respiratory diseases. It has been established previously that ferroptotic cells trigger the innate immune system by releasing inflammation-linked damage-related molecules, and immune cells stimulate the inflammatory response by recognizing the operational mechanism of ferroptosis. Some anti-inflammatory drugs have been shown to inhibit ferroptosis in certain cell models. Conversely, some ferroptosis inhibitors also exert anti-inflammatory effects in certain diseases. The present review evaluated the relationship between ferroptosis and inflammation, as well as the underlying internal mechanism, and provided valuable insights into developing novel treatment strategies for inflammatory diseases and cancer.

Leishmaniasis is an exemplary paradigm of immune evasion, fraught with the perils of limited clinical assistance, escalating costs of treatment and made worse with the lack of suitable vaccine. While drugs remain central to large-scale disease control, the growing emergence of parasite resistance necessitates the need for combination therapy involving host-directed immunological agents. Also, since prolonged disease progression is associated with strong immune suppression of the host, augmentation of host immunity via restoration of the immunoregulatory circuit involving antigen-presenting cells and T-cells, activation of macrophage function and/or CD4⁺ T helper 1 cell differentiation may serve as an ideal approach to resolve severe cases of leishmaniasis. As such, therapies that embody a synergistic approach that involve direct killing of the parasite in addition to elevating host immunity are likely to pave the way for widespread elimination of leishmaniasis in the future. With this review, we aim to recapitulate the various immunotherapeutic agents found to hold promise in antileishmanial treatment both in vitro and in vivo. These include parasite-specific antigens, dendritic cell-targeted therapy, recombinant inhibitors of various components intrinsic to immune cell signaling and agonists or antagonists to immune cells and cytokines. We also summarize their abilities to direct therapeutic skewing of the host cell-immune response and review their potential to combat the disease either alone, or as adjunct modalities.

The ongoing COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global threat. Despite strict control measures implemented worldwide and immunization using novel vaccines, the pandemic continues to rage due to emergence of several variants of SARS-CoV-2 with increased transmission and immune escape. The rapid spread of variants of concern (VOC) in the recent past has created a massive challenge for the control of COVID-19 pandemic via the currently used vaccines. Vaccines that are safe and effective against the current and future variants of SARS-CoV-2 are essential in controlling the COVID-19 pandemic. Rapid production and massive rollout of next-generation vaccines against the variants are key steps to control the COVID-19 pandemic and to help us return to normality. Coordinated surveillance of SARS-CoV-2, rapid redesign of new vaccines and extensive vaccination are needed to counter the current SARS-CoV-2 variants and prevent the emergence of new variants. In this article, we review the latest information on the VOCs and variants of interest (VOIs) and present the information on the clinical trials that are underway on evaluating the effectiveness of COVID-19 vaccines on VOCs. We also discuss the current challenges posed by the VOCs in controlling the COVID-19 pandemic and future strategies to overcome the threat posed by the highly virulent and rapidly transmissible variants of SARS-CoV2.