Shideh Namazi , Vahid Ziaee , Nima Rezaei ,
Volume 73, Issue 6 (9-2015)
Abstract
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease, involves almost all organs such as skin, heart, kidneys and central nervous system. The disease is characterized by vascular and connective tissue inflammation in a recurring pattern of remission and flare. Although the exact pathophysiology of disease has not been fully understood yet, the fundamental defect in SLE is attributed to dysfunction of T lymphocytes in controlling of B-cell that leads to polyclonal activation of B lymphocytes and production a large quantity of autoantibodies against nuclear and cytoplasmic components. These autoantibodies can damage tissues either directly or as a result of immune complex deposits. Several factors are involved in pathogenesis of SLE which can be divided into three major groups, environmental factors, genetic components, and immunological disturbances. They could breakdown body tolerance towards endogenous antigens and cause abnormal immunologic response to the healthy tissue, resulting in tissue damage. SLE occurs more frequently in female than male. It seems that immunological factors have important role in SLE. Inflammation and vascular endothelium irregularities are a number of main pathologies seen in SLE. Cytokines are protein mediators that play an essential role as regulator of innate and adaptive immune response against microbial agents or self-antigens. Influences of cytokines in autoimmune diseases such as SLE are poorly understood. Studies in both experimental animal models of lupus and patients with SLE have revealed a number of cytokine pathways that are important in the disease process. These studies showed that overexpression of inflammatory cytokines increases the proliferation of auto reactive B-cells and results in higher production of autoantibodies. Among them, the role of B-cell activating factor (BAFF), a proliferation-inducing ligand (APRIL), TNF-α, IFN-α, IL-6, IFN-γ, IL-23/IL-17, IL-10, IL-21 are prominent, which is associated with the generation of pathogenic autoantibodies and formation of immune complexes. In this paper, the role of cytokines and their encoding genes are described, while therapeutic applications are also briefly presented.
Davoud Farajzadeh , Parisa Jalali ,
Volume 76, Issue 5 (8-2018)
Abstract
The natural killer group 2D (NKG2D) is a transmembrane protein and a member of the CD94/NKG2 family of C-type lectin-like receptors. NKG2D is encoded by the KLRK1 gene, which is located in the NK-gene complex (NKC) placed on chromosomes 6 and 12 in mice and humans, respectively. NKG2D forms a homodimer structure and binds through ectodomains with its related ligands. Each of its monomers consists of two β-sheets, two α-helices, and four disulfide bands and also contains a β-strand that distinguishes it from other C-type lectin-like receptors. NKG2D ligands are homologs of major histocompatibility complex (MHC) class I molecules in mice and humans. MHC class I chain-related protein A (MICA) and B (MICB) and human cytomegalovirus UL16-binding proteins (ULBP1-6) are recognized by the human NKG2D. In Natural Killer (NK) cells, NKG2D-mediated cytotoxicity can be elicited via two different systems by signaling from immunoreceptor tyrosine-based activation motifs in DAP12 or via a Syk-independent pathway activated by DAP10. Therefore, NKG2D is an activating immunoreceptor which was first recognized on NK cells but subsequently found on γδT cells, CD8+ αβT cells, and macrophages. NKG2D-ligand diversity may facilitate the detection of the presence of a broad range of viruses and may provide protection against rapidly evolving cancers. NKG2D ligand recognition induces and/or improves immune responses to cancer cells. NK cells recognize a wide range of stressed cells. The activation of NKG2D receptor can lead to the lysis of the target cell and the production of various cytokines and chemokines depending on the nature of the stimulation as a result of NK and myeloid-mediated innate immunity and as well as T γδ and CD8+ mediated-adaptive immune system. However, inappropriate expression of NKG2D ligands could cause autoimmune diseases in healthy cells, including rheumatoid arthritis, colitis, celiac disease, multiple sclerosis, alopecia areata, type 1 diabetes, and chronic obstructive pulmonary disease. Therefore, a precise understanding of the structure and function of NKG2D receptor and its interaction with various ligands may lead to the development of strategies to treat autoimmune diseases. Hence, the purpose of this review is to examine the detailed studies on the function of NKG2D receptor and their related ligands.
