IL7, also known as interleukin 7, is a hematopoietic growth factor that belongs to the IL-7/IL-9 family. It is secreted by stromal cells in the bone marrow and thymus. IL7 stimulates the proliferation of lymphoid progenitors. It is important for proliferation during certain stages of B-cell maturation. IL7 and the hepatocyte growth factor (HGF) form a heterodimer that functions as a pre-pro-B cell growth-stimulating factor. It is found to be a cofactor for V(D)J rearrangement of the T cell receptor beta (TCRß) during early T cell development. IL7 can be produced locally by intestinal epithelial and epithelial goblet cells and may serve as a regulatory factor for intestinal mucosal lymphocytes.
Interleukin 7 Receptor alpha (IL-7RA), also known as CD127, is a 75 kDa hematopoietin receptor superfamily member that plays an important role in lymphocyte differentiation, proliferation, and survival. IL-7RA signaling is essential for T-cell development and regulation of naive and memory T-cell homeostasis. Studies from both pathogenic and controlled HIV infection indicate that the containment of immune activation and preservation of CD127 expression are critical to the stability of CD4(+) T cells in infection. A better understanding of the factors regulating CD127 expression in HIV disease, particularly on T(CM) cells, might unveil new approaches exploiting the IL-7/IL-7R receptor pathway to restore T cell homeostasis and promote immune reconstitution in HIV infection. Factors relevant to HIV infection that could potentially decrease CD127 expression on human CD8(+) T cells. CD127 down-regulation may be an important contributor to HIV-associated T-cell dysfunction. In addition to IL-7, IL-7RA also associates with TSLPR to form the functional receptor for thymic stromal lymphopoietin (TSLP) which indirectly regulates T cell development by modulating dendritic cell activation. Mutations in the human IL-7RA gene cause a type of severe combined immunodeficiency in which the major deficiencies are in T cell development, whereas B and NK cells are relatively normal in number. Soluble CD127 (sCD127) appears to play an important role in the immunopathogenesis of several chronic infections, multiple sclerosis, and various cancers.
Interleukin 9 (IL9) is involved in mast cell maturation and the enhancement of IgE production by B cells. Furthermore, linkage data in human and mice have suggested that IL9 may contribute to asthma. IL9R is known to be autosomal in mice, and is X-linked only in primates.The more recent X linkage and more telomeric position of the IL9R gene may explain its autosomal, 'uninactivated' transcriptional status.
IFN gamma, also known as IFNG, is a secreted protein which belongs to the type I I interferon family. IFN gamma is produced predominantly by natural killer and natural killer T cells as part of the innate immune response, and by CD4 and CD8 cytotoxic T lymphocyte effector T cells once antigen-specific immunity develops. IFN gamma has antiviral, immunoregulatory, and anti-tumor properties. IFNG, in addition to having antiviral activity, has important immunoregulatory functions, it is a potent activator of macrophages, and has antiproliferative effects on transformed cells and it can potentiate the antiviral and antitumor effects of the type I interferons. The IFNG monomer consists of a core of six α-helices and an extended unfolded sequence in the C-terminal region. IFN gamma is critical for innate and adaptive immunity against viral and intracellular bacterial infections and for tumor control. Aberrant IFN gamma expression is associated with a number of autoinflammatory and autoimmune diseases. The importance of IFN gamma in the immune system stems in part from its ability to inhibit viral replication directly, and most importantly from its immunostimulatory and immunomodulatory effects. IFNG also promotes NK cell activity.
Interleukin 12 (IL-12) is the founding member of the IL-12 family of heterodimeric cytokines, which have important immunological functions. IL-12 is composed of two disulfide-linkedsubunits of 35 kDa and 40 kDa, respectively. The 35 kDa subunit (p35) is an α-helical protein homologous to IL-6 and GCSF.The 40 kDa subunit(p40) contains one fibronectin type III and one Ig C2-like domain, and has a high degree of structural homology to type I cytokine receptors. Whereas p35 subunit is unique to IL-12,the p40 subunit is also utilized in IL-23.Mature rat p35 is a 194 amino acids (aa) protein that is secreted as a heterodimer linked to p40. It contains three potential N-linked glycosylation sites and shares 86%, and 58% aa sequence identity with mouse and human p35, respectively. Mature rat p40 contains 313 aa and can exist in multiple forms, including monomer, homodimer, heterodimer linked to p19 (forming IL23), and heterodimer linked to p35 (forming IL-12). IL12 facilitates hematopoietic stem cell proliferation, induces NK cell proliferation, and potentiates the expansion and late activation of Th1 CD4+ T cells.
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