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Mesenchymal stem cells (MSC) represent a promising cellular therapy for the treatment of immune-related conditions due to their immunomodulatory properties, which include the capacity to inhibit the proliferation and function of T-cells. Despite the fact that MSC have been the subject of intense investigation as therapeutic agents for diseases in which cellular immune response is exacerbated, the underlying mechanisms of how MSC exert their Tcell suppressive properties remain to be fully understood. Eph surface tyrosine kinase receptors and their ephrin ligands are involved in T-cell development, maturation, activation and proliferation. Recent findings have demonstrated Eph/ephrin interactions as potential mechanisms mediating human MSC inhibition of activated T-cells.Here we highlight the influence of Eph and ephrin molecules in the communication between MSC and T-cells that result in T-cell suppression by MSC. Refereed/Peer-reviewed

Malignant cells produce specific tumor antigen receptors (TAAs), which can be engineered to be recognized by a patient’s own T-cells through the expression of chimeric antigen receptors (CARs). These CAR-T cells represent the latest product of adoptive cellular immunotherapy (ACI). In particular, the engineering of CAR-T cells has been most successful to date in the targeting of CD-19 B-cell associated hematologic malignancies. This review focuses on a general review of the engineering process of CAR-T, difference between the various generations, treatment options, and associated toxicities. To date, most of the literature regarding CAR-T cells is directed towards CD19 to treat Bcell malignancies, including chronic lymphocytic leukemia (CLL), B-cell acute lymphoblastic leukemia (ALL), and non-Hodgkin lymphomas.

Regulatory T cells (Treg), both natural and induced, play an important role in maintaining immune homeostasis. Alterations in the number and functions of Tregs are involved in tumor growth. One of the possible regulatory mechanisms of Treg functional activity involves interaction with major component of extracellular matrix hyaluronan. It has been demonstrated that high molecular weight hyaluronan promotes Treg function via increased expression of FoxP3 and production of IL-10. Moreover, previous research has shown highly enhanced suppressor function of hyaluronan-binding CD4+CD25+ Tregs in mice. Breast cancer is characterized by upregulated production of tumor-associated hyaluronan, therefore we investigated hyaluronan-binding subset of Tregs obtained from peripheral blood of breast cancer patients. As a result, we showed that the majority of peripheral blood Tregs were able to adhere to immobilized hyaluronan, and these cells exerted superior suppressor activity, suggesting a key role in regulatory functions of these cells. The percentage of CD4+FoxP3+ Treg cells binding hyaluronan, as well as CD39+ hyaluronan-binding Tregs were significantly increased in breast cancer patients compared to healthy donors. Enhanced number of the activated Treg cells might play an important role in the suppression of antitumor immunity.

Macrophages (Mϕs) exhibit a sliding scale of functional heterogeneity ranging from pro-inflammatory, immune activatory and anti-tumoral responses to anti-inflammatory, regulatory and pro-tumoral activity. These effector responses are reflected in distinct Mϕ subsets; the M1/classically activated- and M2/alternatively activated subsets. The functional diversity is determined by the combination of Mϕ subset differentiation, activation, signalling and preprogramming in separate monocyte subsets. This diversity in Mϕ subset and functionality is also reflected in mucosal pathologies associated with chronic inflammation (Crohn’s disease, chronic periodontitis) and immunosuppression observed in solid tumours (oral squamous cell carcinoma). The relative functional plasticity between these monocytes and Mϕs represents a realistic therapeutic regimen in the treatment of these Mϕ-driven diseases. This review will discuss the research evidence that is suggestive of the manipulation of Mϕ polarisation plasticity through pre-programming, differentiation, activation and tolerisation in the therapeutic intervention for chronic inflammation and solid tumours.

Myocardial diseases and atherosclerosis are widely considered to be an immune mediated process. Fcγ receptors (FcγRs) contribute to the regulation of immune and inflammatory responses and have been implicated in human cardiovascular lesions. Major cell types involved in the pathogenesis of the diseases express FcγRs and their ligands such as immune complexes and C-reactive protein have been shown to activate FcγRs signal pathway. This review summarizes recent significant progress addressing the various roles of FcγRs in the disease pathogenesis which comes from the studies of FcγRs deficient animal models, clinical investigations and in vitro molecular and cellular studies. These new findings help us appreciate the emerging role of FcγRs in cardiovascular diseases, and suggest FcγRs as a potential therapeutic target for the diseases.

The basic goal of immune system is to defend the host against pathogenic microorganisms and cancers. However, the immune system must also remain tolerant to mutualistic microorganisms and self-tissues. Therefore a critical balance between the destruction of pathogenic insults, and the limiting of collateral damage, must be maintained by the immune system. Immune system balance, or immune homeostasis, greatly depends upon effective targeting of a pathogenic insult, when encountered, followed by a return to steady state once it has been eliminated. Cytokines, which are low molecular weight proteins secreted by numerous cell types, play a critical role in the initiation of immune responses directed against a pathogenic insult and a subsequent return to steady state [1]. Given the critical importance of cytokine biology in immune system function and homeostasis, we have compiled a special issue of the Journal of Clinical and Cellular Immunology entitled: “Cytokine Biology: Cytokines at the interface of Health and Disease.” Within this issue we focus not only on the critical need for cytokines to initiate a proper immune response to pathogenic microorganisms and cancers, but also the deleterious effects of dysregulated cytokine signaling.

Rheumatoid arthritis (RA) is a complex and common systemic autoimmune disease characterized by synovial inflammation and hyperplasia. Multiple proteins, cells, and pathways have been identified to contribute to the pathogenesis of RA. Galectins are a group of lectins that bind to β-galactoside carbohydrates on the cell surface and in the extracellular matrix. They are expressed in a wide variety of tissues and organs with the highest expression in the immune system. Galectins are potent immune regulators and modulate a range of pathological processes, such as inflammation, autoimmunity, and cancer. Accumulated evidence shows that several family members of galectins play positive or negative roles in the disease development of RA, through their effects on T and B lymphocytes, myeloid lineage cells, and fibroblast-like synoviocytes. In this review, we will summarize the function of different galectins in immune modulation and their distinct roles in RA pathogenesis.

Many factors contribute to the pathogenesis of autoimmune diabetes. Targets for treating this debilitating disease will become more apparent by understanding the nature of immune activation. This review examines the possibility of targeting costimulation and discusses the molecules found on the T cell and the antigen-presenting cell (APC) that participate in T-cell activation. The B7-1/B7-2:CD28/cytotoxic T lymphocyte antigen-4 (CTLA-4) pathway has been shown to be crucial in regulating T-cell activation and tolerance. Novel members of the B7-CD28 superfamily have recently been discovered, and they appear to be particularly important for regulating the responses of previously activated T cells. Superimposition of inhibitory signals, such as those delivered by CTLA-4 and the programmed death (PD)-1-PD-1 ligand (PD-L1) pathway, leads to a complex network of positive and negative costimulatory signals, the integration of which modulates immune responses. Furthermore, expression of the B7 homolog B7-H4 on cells in peripheral tissues indicates new mechanisms for regulating T-cell responses. This review focuses on our current understanding of the members of the B7:CD28 superfamily and discusses their therapeutic potential in autoimmune diabetes.

Sepsis is one of the most challenging health problems worldwide. In the USA alone, around three-quarters of a million cases occur every year, and the fatality rate remains between 30% and 50% [1]. A recent report indicates that between 1999 and 2005, sepsis contributed to 6% of all deaths in the United States [2]. Treating sepsis remains problematic, as no effective anti-sepsis drug is currently available.