The BTB-ZF transcription factors

The BTB-ZF (broad-complex, tramtrack and bric-à-brac - zinc finger) proteins are encoded by at least 49 genes in mouse and man and commonly serve as sequence-specific silencers of gene expression. This review will focus on the known physiological functions of mammalian BTB-ZF proteins, which include essential roles in the development of the immune system. We discuss their function in terminally differentiated lymphocytes and the progenitors that give rise to them, their action in hematopoietic malignancy and roles beyond the immune system.     

The BTB-ZF family of transcription factors: key regulators of lineage commitment and effector function development in the immune system

Successful immunity depends upon the activity of multiple cell types. Commitment of pluripotent precursor cells to specific lineages, such as T or B cells, is obviously fundamental to this process. However, it is also becoming clear that continued differentiation and specialization of lymphoid cells is equally important for immune system integrity. Several members of the BTB-ZF family have emerged as critical factors that control development of specific lineages and also of specific effector subsets within these lineages. For example, BTB-ZF genes have been shown to control T cell versus B cell commitment and CD4 versus CD8 lineage commitment. Others, such as PLZF for NKT cells and Bcl-6 for T follicular helper cells, are necessary for the acquisition of effector functions. In this review, we summarize current findings concerning the BTB-ZF family members with a reported role in the immune system.     

Disease causing mutations in the TNF and TNFR superfamilies: Focus on molecular mechanisms driving disease

The tumor necrosis factor (TNF) and TNF receptor (TNFR) superfamilies comprise multidomain proteins with diverse roles in cell activation, proliferation and cell death. These proteins play pivotal roles in the initiation, maintenance and termination of immune responses and have vital roles outside the immune system. The discovery and analysis of diseases associated with mutations in these families has revealed crucial mechanistic details of their normal functions. This review focuses on mutations causing four different diseases, which represent distinct pathological mechanisms that can exist within these superfamilies: autoimmune lymphoproliferative syndrome (ALPS; FAS mutations), common variable immunodeficiency (CVID; TACI mutations), tumor necrosis factor receptor associated periodic syndrome (TRAPS; TNFR1 mutations) and hypohidrotic ectodermal dysplasia (HED; EDA1/EDAR mutations). In particular, we highlight how mutations have revealed information about normal receptor-ligand function and how such studies might direct new therapeutic approaches.     

Semaphorins: a new class of immunoregulatory molecules

The immune and nervous systems play distinct roles in maintaining physiological homeostasis. Recent data indicates that these systems influence one another and share many proteins and pathways that are essential for their normal function and development. Molecules originally shown to be critical for the development of proper immune responses have recently been found to function in the nervous system. Conversely, neuronal guidance cues can modulate immune functions. Although semaphorins were originally identified as axon guidance factors active during neuronal development, several recent studies have identified indispensable functions for these molecules in the immune system. This review provides an overview of the rapidly emerging functions of semaphorins and their receptors in the immune system.     

Towards an understanding of semaphorin signalling in the spinal cord

Semaphorins are a large family of proteins that are classically associated with axon guidance. These proteins and their interacting partners, the neuropilins and plexins are now known to be key mediators in a variety of processes throughout the nervous system ranging from synaptic refinement to the correct positioning of neuronal and glial cell bodies. Recently, much attention has been given to the roles semaphorins play in other body tissues including the immune and vascular systems. This review wishes to draw attention back to the nervous system, specifically focusing on the role of semaphorins in the development of the spinal cord and their proposed roles in the adult. In addition, their functions in spinal cord injury at the glial scar are also discussed.     

Evidence of positive selection at codon sites localized in extracellular domains of mammalian CC motif chemokine receptor proteins

Background  

CC chemokine receptor proteins (CCR1 through CCR10) are seven-transmembrane G-protein coupled receptors whose signaling pathways are known for their important roles coordinating immune system responses through targeted trafficking of white blood cells. In addition, some of these receptors have been identified as fusion proteins for viral pathogens: for example, HIV-1 strains utilize CCR5, CCR2 and CCR3 proteins to obtain cellular entry in humans. The extracellular domains of these receptor proteins are involved in ligand-binding specificity as well as pathogen recognition interactions.     

CIG-DB: the database for human or mouse immunoglobulin and T cell receptor genes available for cancer studies

Background  

Immunoglobulin (IG or antibody) and the T-cell receptor (TR) are pivotal proteins in the immune system of higher organisms. In cancer immunotherapy, the immune responses mediated by tumor-epitope-binding IG or TR play important roles in anticancer effects. Although there are public databases specific for immunological genes, their contents have not been associated with clinical studies. Therefore, we developed an integrated database of IG/TR data reported in cancer studies (the Cancer-related Immunological Gene Database [CIG-DB]).     

The interaction between maternal stress and the ontogeny of the innate immune system during teleost embryogenesis: implications for aquaculture practice

The barrier defences and acellular innate immune proteins play critical roles during the early‐stage fish embryos prior to the development of functional organ systems. The innate immune proteins in the yolk of embryos are of maternal origin. Maternal stress affects the maternal‐to‐embryo transfer of these proteins and, therefore, environmental stressors may change the course of embryo development, including embryonic immunocompetency, via their deleterious effect on maternal physiology. This review focuses on the associations that exist between maternal stress, maternal endocrine disturbance and the responses of the acellular innate immune proteins of early‐stage fish embryos. Early‐stage teleostean embryos are dependent upon the adult female for the formation of the zona pellucida as an essential barrier defence, for their supply of nutrients, and for the innate immunity proteins and antibodies that are transferred from the maternal circulation to the oocytes; maternally derived hormones are also transferred, some of which (such as cortisol) are known to exert a suppressive action on some aspects of the immune defences. This review summarizes what is known about the effects of oocyte cortisol content on the immune system components in early embryos. The review also examines recent evidence that embryonic cells during early cleavage have the capacity to respond to increased maternal cortisol transfer; this emphasizes the importance of maternal and early immune competence on the later life of fishes, both in the wild and in intensive culture.     

不同培养基上繁殖的昆虫病原线虫格氏线虫表皮蛋白的差异

表皮蛋白(surface coat proteins, SCPs)是格氏线虫Steinernema glaseri克服寄主免疫系统的关键因素, 能够抑制昆虫免疫反应, 促进线虫的侵染。为了进一步研究表皮蛋白抑制昆虫免疫的作用机理和线虫与寄主间的相互关系, 我们比较分析了不同培养基繁殖的格氏线虫表皮蛋白的差异。我们用人工培养基和大蜡螟Galleria mellonella末龄（5龄）幼虫分别培养得到格氏线虫侵染期幼虫, 利用酒精提取表皮蛋白。SDS-PAGE和非变性PAGE分析显示, 大蜡螟来源的格氏线虫的表皮蛋白具有更多的蛋白条带。体外和体内的裂解血细胞实验表明, 大蜡螟来源的格氏线虫的表皮蛋白表现出强烈的裂解血细胞活性, 而人工培养基来源的格氏线虫的表皮蛋白活力不明显; 且具有裂解血细胞活性的表皮蛋白为诱导表达型蛋白。不同培养基来源的格氏线虫的表皮蛋白组成的差异和活性的不同, 表明格氏线虫表皮蛋白的产生受线虫培养条件影响较大。     

The immunomodulatory effects of tachykinins and their receptors

Tachykinins (TKs) are a family of neuropeptides mainly expressed by neuronal and non-neuronal cell types, especially immune cells. Expression of TKs receptors on immune cell surfaces, their involvement in immune-related disorders, and therefore, understanding their immunomodulatory roles have become of particular interest to researchers. In fact, the precise understanding of TKs intervention in the immune system would help to design novel therapeutic approaches for patients suffering from immune disorders. The present review summarizes studies on TKs function as modulators of the immune system by reviewing their roles in generation, activation, development, and migration of immune cells. Also, it discusses TKs involvement in three main cellular mechanisms including inflammation, apoptosis, and proliferation.     

GPI7-mediated glycosylphosphatidylinositol anchoring regulates appressorial penetration and immune evasion during infection of Magnaporthe oryzae

Glycosylphosphatidylinositol (GPI) anchoring plays key roles in many biological processes by targeting proteins to the cell wall; however, its roles are largely unknown in plant pathogenic fungi. Here, we reveal the roles of the GPI anchoring in Magnaporthe oryzae during plant infection. The GPI-anchored proteins were found to highly accumulate in appressoria and invasive hyphae. Disruption of GPI7, a GPI anchor-pathway gene, led to a significant reduction in virulence. The Δgpi7 mutant showed significant defects in penetration and invasive growth. This mutant also displayed defects of the cell wall architecture, suggesting GPI7 is required for cell wall biogenesis. Removal of GPI-anchored proteins in the wild-type strain by hydrofluoric acid (HF) pyridine treatment exposed both the chitin and β-1,3-glucans to the host immune system. Exposure of the chitin and β-1,3-glucans was also observed in the Δgpi7 mutant, indicating GPI-anchored proteins are required for immune evasion. The GPI anchoring can regulate subcellular localization of the Gel proteins in the cell wall for appressorial penetration and abundance of which for invasive growth. Our results indicate the GPI anchoring facilitates the penetration of M. oryzae into host cells by affecting the cell wall integrity and the evasion of host immune recognition.     

Role of toll-like receptors gene polymorphism in hepatocellular carcinoma

Abstract

Toll-like receptors (TLRs), evolutionarily conserved innate, play important roles in the development of autoimmunity. TLRs proteins are localized on the cell surface or in endosomes and play critical roles in innate immune responses against different pathogens. Aberrant stimulation of the innate immune system through intracellular TLRs may lead to hyperactive immune responses and contribute to the pathogenesis of hepatocellular carcinoma (HCC). HCC is the seventh most common cancer and the third leading cause of cancer deaths worldwide, and innate immune takes a most important role in HCC. There was no review to sum up the role of TLRs gene polymorphism in HCC. This review was performed to sum up the role of TLRs gene polymorphism in HCC.     

Immune plexins and semaphorins: old proteins,new immune functions

Plexins and semaphorins are a large family of proteins that are involved in cell movement and response. The importance of plexins and semaphorins has been emphasized by their discovery in many organ systems including the nervous (Nkyimbeng-Takwi and Chapoval, 2011; McCormick and Leipzig, 2012; Yaron and Sprinzak, 2012), epithelial (Miao et al., 1999; Fujii et al., 2002), and immune systems (Takamatsu and Kumanogoh, 2012) as well as diverse cell processes including angiogenesis (Serini et al., 2009; Sakurai et al., 2012), embryogenesis (Perala et al., 2012), and cancer (Potiron et al., 2009; Micucci et al., 2010). Plexins and semaphorins are transmembrane proteins that share a conserved extracellular semaphorin domain (Hota and Buck, 2012). The plexins and semaphorins are divided into four and eight subfamilies respectively based on their structural homology. Semaphorins are relatively small proteins containing the extracellular semaphorin domain and short intracellular tails. Plexins contain the semaphorin domain and long intracellular tails (Hota and Buck, 2012). The majority of plexin and semaphorin research has focused on the nervous system, particularly the developing nervous system, where these proteins are found to mediate many common neuronal cell processes including cell movement, cytoskeletal rearrangement, and signal transduction (Choi et al., 2008; Takamatsu et al., 2010). Their roles in the immune system are the focus of this review.     

The complement system in teleosts

Complement, an important component of the innate immune system, is comprised of about 35 individual proteins. In mammals, activation of complement results in the generation of activated protein fragments that play a role in microbial killing, phagocytosis, inflammatory reactions, immune complex clearance, and antibody production. Fish appear to possess activation pathways similar to those in mammals, and the fish complement proteins identified thus far show many homologies to their mammalian counterparts. Because information about complement proteins, regulatory proteins, and complement receptors in fish is far from complete, it is unclear whether all the complement functions that have been identified in mammals also occur in fish. However, it has been clearly demonstrated that fish complement can lyse foreign cells and opsonise foreign organisms for destruction by phagocytes. There are also indications that complement fragments participate in inflammatory reactions. Fish possess multiple isoforms of several complement proteins, such as C3 and factor B. It has been hypothesised that the function of this diversity in complement proteins serves to expand their innate immune recognition capacity and response. Understanding the functions of complement in fish and the roles the individual proteins, including the various isoforms, play in host defence, is important not only for understanding the evolution of this system but also for the development of new strategies in fish health management.     

Domain architecture evolution of pattern-recognition receptors

In animals, the innate immune system is the first line of defense against invading microorganisms, and the pattern-recognition receptors (PRRs) are the key components of this system, detecting microbial invasion and initiating innate immune defenses. Two families of PRRs, the intracellular NOD-like receptors (NLRs) and the transmembrane Toll-like receptors (TLRs), are of particular interest because of their roles in a number of diseases. Understanding the evolutionary history of these families and their pattern of evolutionary changes may lead to new insights into the functioning of this critical system. We found that the evolution of both NLR and TLR families included massive species-specific expansions and domain shuffling in various lineages, which resulted in the same domain architectures evolving independently within different lineages in a process that fits the definition of parallel evolution. This observation illustrates both the dynamics of the innate immune system and the effects of “combinatorially constrained” evolution, where existence of the limited numbers of functionally relevant domains constrains the choices of domain architectures for new members in the family, resulting in the emergence of independently evolved proteins with identical domain architectures, often mistaken for orthologs.     

Characterisation of monoclonal antibodies to the TNF and TNF receptor families

Tumour necrosis factor (TNF) family ligands and their corresponding receptors play important roles in the immune system and are involved in immune regulation such as lymphoid development, cell proliferation, differentiation, activation and death. Antibodies against these ligands and receptors together with Fc-fusion proteins, have been particularly useful as immunological tools in addressing the underlying involvement of these proteins in these contexts and furthermore, have given us hope in using them as potential therapeutic agents. Over last few years, there have been many additions to these ever-growing TNF family ligands and their receptors. Here, we have generated and characterised a set of monoclonal antibodies, together with mAbs from the HLDA workshop, against DcR1, DcR2, DR4, DR5, TRAIL, APRIL, BAFF, BAFF-R, BCMA, and TACI, which may be useful in phenotypic and functional studies of the role of TNF and TNF receptor family in immune function and regulation in relation to health and disease.     

The pathogenesis of thyroid autoimmune diseases: New T lymphocytes – Cytokines circuits beyond the Th1−Th2 paradigm

Autoimmune thyroid disease (AITD) is one of the most common organ-specific autoimmune disorders. It mainly manifests as Hashimoto's thyroiditis (HT) and Graves’ disease (GD). HT is characteristic of hypothyroidism resulting from the destruction of the thyroid while GD is characteristic of hyperthyroidism due to excessive production of thyroid hormone induced by thyrotropin receptor-specific stimulatory autoantibodies. T lymphocytes and their secretory cytokines play indispensable roles in modulating immune responses, but their roles are often complex and full of interactions among distinct components of the immune system. Dysfunction of these T cells or aberrant expressions of these cytokines can cause the breakdown of immune tolerance and result in aberrant immune responses during the development of AITDs. This review summarizes recently identified T subsets and related cytokines and their roles in the pathogenesis of AITDs with the hope to provide a better understanding of the precise roles of notably identified T subsets in AITDs and facilitate the discovery of functional molecules or novel immune therapeutic targets for AITDs.