IL-33, also known as NF-HEV and DVS 27, is a 30 kDa proinflammatory protein that may also regulate gene transcription. DVS 27 was identifed as a gene that is upregulated in vasospastic cerebral arteries. NF-HEV was described as a nuclear factor that is preferentially expressed in the endothelial cells of high endothelial venules relative to endothelial cells from other tissues. IL-33 was identified based on sequence and structural homology with IL-1 family cytokines. DVS 27, NF-HEV, and IL-33 share 100% amino acid sequence identity. IL-33 is constitutively expressed in smooth muscle and airway epithelia. It is upregulated in arterial smooth muscle, dermal fibroblasts, and keratinocytes following IL-1 alpha or IL-1 beta stimulation. Similar to IL-1, IL-33 can be cleaved in vitro by caspase-1, generating an N-terminal fragment that is slightly shorter than the C-terminal fragment. The N-terminal portion of full length IL-33 contains a predicted bipartite nuclear localization sequence and a homeodomain-like helix-turn-helix DNA binding domain. By immunofluorescence, full length IL-33 localizes to the nucleus in HUVECs and transfectants. The C-terminal fragment, corresponding to mature IL-33, binds and triggers signaling through mast cell IL-1 R4/ST2L, a longtime orphan receptor involved in the augmentation of Th2 cell responses. A ternary signaling complex is formed by the subsequent association of IL-33 and ST2L with IL-1R AcP. Stimulation of Th2 polarized lymphocytes with mature IL-33 in vitro induces IL-5 and IL-13 secretion. In vivo administration of mature IL-33 promotes increased production of IL-5, IL-13, IgE, and IgA, as well as splenomegaly and inflammatory infiltration of mucosal tissues. Full length and mature human IL-33 share 52 ‑ 58% aa sequence identity with mouse and rat IL-33. Human IL-33 shares less than 20% aa sequence identity with other IL-1 family proteins.
Interleukin-1 family member 8(IL1F8) also known as IL36B, is a member of the interleukin 1(IL-1) cytokine family. IL1F8 may contain a 12-stranded beta-trefoil structure. Until recently, the IL-1 family of cytokines includes four members, with three having pro-inflammatory effects such as IL1F8 and the fourth member being an IL-1 receptor antagonist (IL-1Ra). IL-1 family members exert their effects through binding to receptors that belong to the IL-1 receptor (IL-1R) family. IL1F8 exerts proinflammatory effects in primary human joint cells. Joint and serum IL-1F8 protein levels did not correlate with inflammation, but they were high in some human serum samples tested, including samples from patients with rheumatoid arthritis. IL1F8 also activated NK-κB.
The protein encoded by this gene is a member of the interleukin 1 cytokine family. The activity of this cytokine is mediated by interleukin 1 receptor-like 2 (IL1RL2/IL1R-rp2), and is specifically inhibited by interleukin 1 family, member 5 (IL1F5/IL-1 delta). Interferon-gamma, tumor necrosis factor-alpha and interleukin 1, beta (IL1B) are reported to stimulate the expression of this cytokine in keratinocytes. The expression of this cytokine in keratinocytes can also be induced by a contact hypersensitivity reaction or herpes simplex virus infection. This gene and eight other interleukin 1 family genes form a cytokine gene cluster on chromosome 2. Two alternatively spliced transcript variants encoding different isoforms have been found for this gene.
CD123 is the 70 kD transmembrane α chain of the IL-3 receptor. Alone, CD123 binds IL-3 with low affinity; when CD123 associates with CDw131 (common β chain), it binds IL-3 with high affinity. CD123 does not transduce intracellular signals upon binding IL-3 and requires the β chain for this function. CD123 is expressed by myeloid precursors, macrophages, dendritic cells, mast cells, basophils, megakaryocytes, and some B cells.
Interleukin-4 (IL-4), also known as B cell-stimulatory factor-1, is a monomeric, approximately 13 kDa‑18 kDa Th2 cytokine that shows pleiotropic effects during immune responses . It is a glycosylated polypeptide that contains three intrachain disulfide bridges and adopts a bundled four alpha -helix structure
IL4 is a cytokine produced by CD4+ T cells in response to helminthes and other extracellular parasites. It promotes the proliferation and differentiation of antigen presenting cells. IL4 also plays a pivotal role in antibody isotype switching and stimulates the production of IgE. This cytokine has been applied in the treatment of autoimmune disorder like multiple myeloma, cancer, psoriasis, and arthritis. IL4 has also been extensively applied to inhibit detrimental effect of Th1. It may promote the growth of epithelial tumors by mediating increased proliferation and survival.
This gene encodes a cytokine that acts as a growth and differentiation factor for both B cells and eosinophils. The encoded cytokine plays a major role in the regulation of eosinophil formation, maturation, recruitment and survival. The increased production of this cytokine may be related to pathogenesis of eosinophil-dependent inflammatory diseases. This cytokine functions by binding to its receptor, which is a heterodimer, whose beta subunit is shared with the receptors for interleukine 3 (IL3) and colony stimulating factor 2 (CSF2/GM-CSF). This gene is located on chromosome 5 within a cytokine gene cluster which includes interleukin 4 (IL4), interleukin 13 (IL13), and CSF2 . This gene, IL4, and IL13 may be regulated coordinately by long-range regulatory elements spread over 120 kilobases on chromosome 5q31.
The protein encoded by this gene is a receptor for interleukin 7 (IL7). This protein has been shown to play a critical role in V(D)J recombination during lymphocyte development. Defects in this gene may be associated with severe combined immunodeficiency (SCID).
Interleukin enhancer-binding factor 3 (ILF3) is a double-stranded RNA (dsRNA) binding protein that complexes with other proteins, dsRNAs, small noncoding RNAs, and mRNAs to regulate gene expression and stabilize mRNAs. This protein (NF90, ILF3) forms a heterodimer with a 45 kDa transcription factor (NF45, ILF2) required for T-cell expression of interleukin 2. This complex has been shown to affect the redistribution of nuclear mRNA to the cytoplasm. Knockdown of NF45 or NF90 protein retards cell growth, possibly by inhibition of mRNA stabilization. In contrast, an isoform (NF110) of this gene that is predominantly restricted to the nucleus has only minor effects on cell growth when its levels are reduced. Alternative splicing results in multiple transcript variants encoding distinct isoforms. ILF3 exists main two isoforms NFAR-1 (90 kDa) and -2 (110 kDa). Upon viral infection, ILF3 accumulates in the cytoplasm and participates in the innate antiviral response.
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