Daftar Lengkap Sitokin 1-38 dan Berbagai Fungsinya

Interleukins (IL) adalah sekelompok sitokin (protein yang disekresikan dan molekul sinyal) yang pertama kali diekspresikan oleh sel darah putih (leukosit). IL dapat dibagi menjadi empat kelompok besar berdasarkan fitur struktural yang membedakan. Namun, kesamaan urutan asam amino mereka agak lemah (biasanya 15-25% identitas). Genom manusia menyandi lebih dari 50 interleukin dan protein terkait.

Fungsi sistem kekebalan tubuh sebagian besar tergantung pada interleukin, dan kekurangan yang jarang dari beberapa dari mereka telah dijelaskan, semuanya menampilkan penyakit autoimun atau defisiensi imun. Mayoritas interleukin disintesis oleh helper limfosit T CD4, juga melalui monosit, makrofag, dan sel endotel. Mereka mempromosikan pengembangan dan diferensiasi limfosit T dan B, dan sel hematopoietik.

Reseptor interleukin pada astrosit di hippocampus juga diketahui terlibat dalam pengembangan memori spasial pada tikus.

Nama “interleukin” dipilih pada tahun 1979, untuk menggantikan berbagai nama yang berbeda yang digunakan oleh kelompok penelitian yang berbeda untuk menunjuk interleukin 1 (faktor pengaktif limfosit, protein mitogenik, faktor penggantian sel-T III, faktor pengaktifan sel-B, diferensiasi sel-B, diferensiasi sel-B faktor, dan “Heidikine”) dan interleukin 2 (TSF, dll.). Keputusan ini diambil selama Lokakarya Limfokin Internasional Kedua di Swiss (27-31 Mei 1979 di Ermatingen).

Istilah interleukin berasal dari (inter-) “sebagai sarana komunikasi”, dan (-leukin) “berasal dari kenyataan bahwa banyak dari protein ini diproduksi oleh leukosit dan bertindak atas leukosit”. Namanya adalah benda peninggalan; Sejak itu telah ditemukan bahwa interleukin diproduksi oleh berbagai macam sel tubuh. Istilah ini diciptakan oleh Dr Vern Paetkau, Universitas Victoria.

Beberapa interleukin diklasifikasikan sebagai limfokin, sitokin yang diproduksi limfosit yang memediasi respons imun.

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Sitokin dan fungsinya
Sitokine Struktur Ukuran(berat molekul) Reseptors Sumber sel Target Sel Fungsi mayor
IL-1α and IL-1β Heterodimer 17 kDa IL-1 type 1 receptor, IL-1 type 2 receptor Macrophages, monocytes, lymphocytes, keratinocytes, microglia, megakaryocytes, neutrophils, fibroblasts, synovial lining cells T cells, fibroblasts, epithelial and endothelial cells Induction of proinflammatory proteins; hematopoiesis; differentiation TH17 cells; development of IL-10–producing Breg cells in mouse spleens and mesenteric lymph nodes
IL-1Ra (antagonist) Heterodimer 16.1-20 kDa IL-1 type 1 receptor, IL-1 type 2 receptor Monocytes, macrophages, fibroblasts, neutrophils, endothelial and epithelial cells, and keratinocytes T cells, fibroblasts, epithelial and endothelial cells Antagonism of IL-1
IL-2 Monomer 15.5 kDa IL-2R CD4+ and CD8+ activated T cells, DCs, NK and NKT cells, mast cells, and ILCs CD4+ and CD8+ T cells, NK and B cells, and ILCs Proliferation of effector T and B cells; development of Treg cells; differentiation and proliferation of NK cells; growth factor for B cells and stimulus for antibody synthesis; proliferation and cytokine production in ILCs
IL-3 Monomer 15 kDa IL-3 receptor α + β c (CD131) T cells, macrophages, NK cells, mast cells, eosinophils, stromal cells Erythroid progenitors, granulocytes, macrophages progenitors, CD34+ progenitor cells, basophils, eosinophils, megakaryocytes, monocytes, Treg and endothelial cells Hematopoietic growth factor; activation of basophils and eosinophils; differentiation of DCs and Langerhans cells; enhancement of IL-2–induced proliferation and differentiation of B cells; improvement of antigen uptake; phagocytosis in macrophages
IL-4 Monomer 15 kDa IL-4R type I, IL-4R type II TH2 cells, basophils, eosinophils, mast cells, NKT cells and γ/δ T cells T and B cells Induction of TH2 differentiation; IgE class-switching; upregulation of class II MHC expression on B cells; upregulation of CD23 and IL-4R; survival factor for B and T cells; role in tissue adhesion and inflammation
IL-5 Homodimer 15 kDa IL-5R TH2 cells, activated eosinophils and masts cells, TC2 cells, γδ T cells, NK and NK T cells and CD4c-KitCD3εIL2Rα (Peyer patches), ILC2s Eosinophils, basophils and mast cells, Treg cells, neutrophils and monocytes Differentiation and function of myeloid cells; increment of eosinophils chemotactic activity and adhesion capacity; involvement in remodeling and wound healing
IL-6 Homodimer 19-26 kDa IL-6R (sIL-6R) gp130 Endothelial cells, fibroblasts, monocytes/macrophages, T cells, B cells, granulocytes, smooth muscle cells, eosinophils, chondrocytes, osteoblasts, mast cells, glial cells, and keratinocytes Hepatocytes, leukocytes, T cells, B cells, hematopoietic cells Induction of acute-phase proteins in hepatocytes; leukocyte trafficking and activation; T-cell differentiation, activation, and survival; B-cell differentiation and production of IgG, IgM, and IgA; hematopoiesis; involvement in osteoclastogenesis and bone resorption and recruitment of mesenchymal vascular cells; neoangiogenesis in vivo; synovial fibroblast proliferation and cartilage degradation; survival of cholinergic neurons and induction of adrenocorticotropic hormone synthesis
IL-7 Monomer 25 kDa IL-7R and sIL-7R Epithelial cells, keratinocytes, DCs, B cells, and monocytes/macrophages Developing B and T lymphocytes, mature T cells, NK cells, and ILCs Proliferation of pre-B and pro-B cells (mice); megakaryocyte maturation; V(D)J recombination; naive T-cell survival; proliferation of thymocytes; development and maintenance of ILCs; synthesis induction of inflammatory mediators in monocytes
IL-8 Homodimer 16 kDa CXCR1 and CXCR2 Monocytes, macrophages, neutrophils, lymphocytes, endothelial cells, epithelial cells, fibroblasts, keratinocytes, chondrocytes, synovial cells, hepatocytes, smooth muscle and skeletal muscle cells Neutrophils, NK cells, T cells, basophils, eosinophils, mast cells, monocytes, and endothelial cells Chemoattractant for neutrophils, NK cells, T cells, basophils, and eosinophils; mobilization of hematopoietic stem cells; angiogenesis
IL-9 Monomer 14 kDa IL-9R TH2, TH9, TH17, and Treg cells, mast cells, eosinophils, ILCs B, T, and mast cells; hematopoietic cells; airway epithelial cells; airway smooth muscle cells; and intestinal epithelial cells T and mast cell growth factor; inhibition of TH1- cytokines; proliferation of CD8+ T cells and mast cells; IgE, chemokine, and mucus production in bronchial epithelial cells
IL-10 Homodimer 20.5 kDa (predicted size of precursor protein) 18.6 kDa (predicted size mature protein, monomer) IL-10R1/IL-10R2 complex T cells, B cells, monocytes, macrophages, and DCs Macrophages, monocytes, T cells, B cells, NK cells, mast cells, DCs, and granulocytes Immunosuppressive effect through APCs or direct effects on T-cell subsets; suppression of IgE and induction of IgG by B cells in human subjects
IL-11 Monomer 19 kDa IL-11Rα + gp130 Bone marrow cells, fibroblasts, epithelial cells, endothelial cells, vascular smooth muscle cells, synoviocytes, osteoblasts Myeoloid, erythroid, and megakaryocyte progenitors, osteoclasts, epithelial cells, hepatocytes, macrophages, neurons Growth factor for myeoloid, erythroid, megakaryocyte progenitors and plasmacytoma cells; protection of epithelial cells and connective tissue; induction of acute-phase proteins; inhibition of monocytes and macrophage activity; promotion of neuronal development; bone remodeling, by stimulation of osteoclasts and inhibition of osteoblasts
IL-12 (p35/p40) Heterodimer 35 kDa (IL-12a p35) + 40 kDa (IL12b p40) IL-12Rβ1 and IL-12Rβ2 Monocytes, macrophages, neutrophils, microglia, DCs, B cells T cells (TH1 cells), NK cells Development and maintenance of TH1 cells; activation of NK cells; support of DC maturation; induction of cytotoxicity
IL-13 Monomer 10 kDa IL-13R1α1 and IL-13R1α2 T, NKT, and mast cells; basophils and eosinophils; and ILCs B cells, mast cells, epithelial cells, eosinophils, smooth muscle cells, and macrophages Switching to IgG4 and IgE, upregulation of CD23, MHC class II on B cells, and induction of CD11b, CD11c, CD18, and CD29; CD23 and MHC class II on monocytes; activation of eosinophils and mast cells; recruitment and survival of eosinophils; defense against parasite infections
IL-14 Monomer 53 kDa IL-14R T cells, T-cell clones, B-lineage and T-lineage lymphoma cell lines B cells, certain leukemia cells Proliferation of activated B cells
IL-15 Monomer 14-15 kDa IL-15R Monocytes, macrophages, DCs and activated CD4+ T cells, keratinocytes, skeletal muscle cells, fibroblasts, various epithelial cells, bone marrow stromal cells, nerve cells NK cells, NKT cells, monocytes, macrophages, DCs, neutrophils, eosinophils, mast cells, T cells and B cells T-cell activation; proliferation and activation of NK cells; differentiation of γ/δ T cells; homeostasis of CD8+ memory, NK, and NKT cells; enhancement of TH2 differentiation; prevention of neutrophils and eosinophils from apoptosis
IL-16 Homotetramer 56 kDa CD4 T cells, eosinophils, mast cells, eosinophils, monocytes, DCs, fibroblasts, epithelial cells, synoviocytes T cells, monocytes, macrophages, DCs, eosinophils, mast cells Modulation of T-cell response; chemoattractant for CD4+ T cells, CD8+ T cells, monocytes, mast cells, and eosinophils
IL-17A Cysteine knot, homodimer or heterodimer 35 kDa IL-17RA (= IL-17R) TH17 cells, CD8+ T cells, NK cells, NKT cells, γδ T cells, neutrophils, ILCs Epithelial/endothelial cells, fibroblasts, osteoblasts, monocytes, macrophages, B and T lymphocytes, myelomonocytic cells and marrow stromal cells Induction of proinflammatory cytokines, chemokines, and metalloproteases; recruitment and activation of neutrophils
IL-17B,C,D Cysteine knot, homodimer 41, 40, and 52 kDa For IL-17 B: IL-17RB (= IL-17H1, IL-25R) For IL-17C: IL-17RA to IL-17RE For IL-17D: SEF IL-17B: neuronal cells, chondrocytes; IL-17C: mucosal epithelial cells; IL-17D: resting B and T cells, skeletal muscle, brain, adipose tissue, heart, lung, and pancreas Monocytes, endothelial cells, myofibroblasts, epithelial cells Induction of antimicrobial peptides, proinflammatory cytokines, chemokines. and metalloproteases; IL-17B: chondrogenesis and osteogenesis; IL-17C: influence on intestinal barrier function; IL-17D: suppression of myeloid progenitor cell proliferation
IL-17F Cysteine knot, homodimer or heterodimer 44 kDa IL-17RA (= IL-17R) and IL-17RC (= IL-17RL) TH17 cells, CD8+ T cells, NK cells, NKT cells, γδ T cells neutrophils, basophils, mast cells, monocytes Epithelial/endothelial cells, fibroblasts, osteoblasts, monocytes, macrophages, B and T lymphocytes, myelomonocytic cells and marrow stromal cells Induction of proinflammatory cytokines, chemokines, and metalloproteases; recruitment and activation of neutrophils
IL-18 Heterodimer 22.3 kDa IL-18 receptor Macrophages, DCs, epithelial cells, chondrocytes, osteoblasts, Kupffer cells, keratinocytes, astrocytes, renal tubular epithelial cells T cells, NK cells, macrophages, epithelial cells, chondrocytes Induction of IFN-γ in the presence of IL-12; enhancement of NK cell cytotoxicity, promoting TH1 or TH2 cell responses depending on cytokine milieu
IL-19 Monomer 20.5 kDa: predicted size of precursor; 17 kDa: predicted size of mature protein; 35-40 kDa: found in transfected cells, glycosylated IL-20R1/IL-20R2 Monocytes, keratinocytes, endothelial and epithelial cells, B cells Keratinocytes Induction of TH2 cytokines; enhanced production of IL-6, TNF-α, and IL-10 in monocytes
IL-20 Monomer 20 kDa (predicted size of precursor), 17.5 kDa (predicted size of mature protein) IL-20R1/IL-20R2 and IL-22R1/IL-20R2 Monocytes, keratinocytes, epithelial and endothelial cells Keratinocytes, monocytes, epithelial cells, and stromal cells in skin, lung, pancreas, and breast tissues Role in skin biology
IL-21 Four-helix bundle, monomer 15 kDa IL-21R T cells (predominantly TH17 and TH9), NK T cells CD4+ T cells, CD8+ T cells, B cells, DCs, macrophages, keratinocytes B-cell proliferation, differentiation, and survival; T-cell growth factor; NKT cell proliferation when combined with either IL-2 or IL-15
IL-22 Six anti-parallel α-helices, monomer 23 kDa IL-22R Activated T cells (predominantly TH17 and TH22 cells), NKT cells, activated NK cells, lymphoid tissue-inducer cells, ILCs Keratinocytes and epithelial cells of kidney, small intestine, liver, colon, lung, and particularly pancreas and skin Pathogen defense; wound healing; tissue reorganization
IL-23 (p19+p40) Heterodimer IL-12b p40 = 40 kDa, IL-23 p19 = 19 kDa IL-23R Phagocytic cells, macrophages, and activated DCs from peripheral tissues, including the skin, intestinal mucosa, and lungs T cells (TH17 cells), NK and NKT cells, eosinophils, monocytes, macrophages, DCs, and epithelial cells Stimulation of production of proinflammatory IL-17; enhancement of T-cell proliferation and promotion of memory T cells; activation of NK cells; regulation of antibody production
IL-24 Homodimer and monomer 23.8 kDa (predicted size of unprocessed precursor), 18 kDa (unglycosylated mature protein), 35 kDa (observed size of secreted IL-24, glycosylated) IL-20R1/IL-20R2 and IL-22R1/IL-20R2 Melanocytes, T cells, monocytes, normal human epidermal keratinocytes, B cells Cancer cells Tumor suppression
IL-25 (IL-17E) Homodimer 19 kDa IL-17RA and IL-17RB TH2 cells, mast and epithelial cells, eosinophils, and basophils from atopic subjects TH2 memory cells, fibroblasts, basophils, NKT cells, macrophages, and ILC2s Induction of TH2 responses and inhibition of both TH1 and TH17 cell responses; induction of IgE, IgG1, IL-4, IL-5, IL-13, and IL-9 production
IL-26 Six α-helices, homodimer 38 kDa IL-10R2 chain and IL-20R1 chain Memory T cells, NK cells, activated TH17 cells Epithelial cells, binds heparin Activation and regulation of epithelial cells
IL-27 (p28+EBI3) Heterodimer IL-27a p28 = 28 kDa; IL-27b EBI-3 = 25.4 kDa WSX-1 and gp130 Activated DCs, macrophages, epithelial cells T cells, NK cells Induction of T-bet, promoting TH1 cell differentiation; inhibition of TH17 cells response through STAT1
IL-28A/B/IL29 (IFN-λ family) Monomer IL-28A = 22.3 kDa; IL-28B = 22.2 kDa; IL-29 = 21.9 kDa IL-28R1/IL-10R2 Nucleated cell types, particularly DCs, in response to viral infection Tissue-resident cells, primary monocytes, myeloid and plasmacytoid DCs, and CD4+ cells Downregulation of TH2 response and upregulation of TH1 response; induction of tolerogenic DCs and consequent promotion and expansion of Treg cells
IL-30 (p28 subunit of IL-27) Heterodimer 28 kDa Prevention and treatment of cytokine-induced liver injury
IL-31 Four-helix bundle 24 kDa IL-31RA/OSMRβ Activated CD4+ T cells (mainly TH2) and CD8+ T cells, monocytes, macrophages, DCs, mast cells, keratinocytes, and fibroblasts Keratinocytes, epithelial cells, dorsal root ganglia, eosinophils, mast cells, basophils, and monocytes Induction of IL-6, IL-8, CXCL1, CXCL8, CCL2, and CCL8 production in eosinophils; upregulation of chemokine mRNA expression in keratinocytes and induction of growth factor and chemokine expression in epithelial cells; inhibition of proliferation and apoptosis in epithelial cells
IL-32 Unknown 14.9-26.6 kDa Unknown Monocytes, macrophages, NK cells, T cells, epithelial cells Macrophages, DCs, T cells, PBMCs, monocytes Induction of TNF-α, IL-8, and IL-6 and apoptosis of epithelial cells
IL-33 β-Trefoil fold 30 kDa (active form = 18 kDa) ST2 Necrotic cells, nuocytes, and fibroblasts on mechanical stress; stromal cells on cell damage; epithelial cells Basophils, mast cells, eosinophils, DCs, macrophages, NK cells, NKT cells, T lymphocytes, B lymphocytes, endothelial cells, epithelial cells, fibroblasts, ILCs Transcriptional repressor activity; induction of TH2-type inflammation on mucosal tissues; maturation factor for bone marrow–derived DCs accompanied by the release of proinflammatory cytokines; enhanced integrin expression in basophils and eosinophils; inducer of ILCs
IL-34 Homodimer 39-kDa monomers Colony-stimulating factor 1 receptor Heart, brain, liver, kidney, spleen, thymus, testes, ovary, small intestine, prostate, and colon; most abundant in spleen Monocytes, macrophages Regulator of myeloid lineage differentiation, proliferation, and survival; microglial proliferation
IL-35 (p35+EBI3) Heterodimer 60 kDa IL-12Rβ2/gp130; IL-12Rβ2/IL-12Rβ2; gp130/gp130 Treg cells, monocytes, vascular endothelial cells, smooth muscle cells, and epithelial cells NK cells and activated T cells Reduction of effector T-cell proliferation; increase of IL-10 production and Treg cell proliferation
IL-36 IL-36Ra Internal endothelial tissues and skin, bone marrow–derived macrophages Keratinocytes and other epithelial barriers; at lower levels on DCs, naive CD4+ T cells, differentiated TH1 and TH2 cells; very low levels on TH17 cells Promotion of the early inflammatory response to tissue injury or infection
IL-37 Unknown 17-24 kDa IL-18Rα and IL-18BP Monocytes, tonsil plasma cells, breast carcinoma cells, some colon carcinoma cells, melanomas, and lung carcinomas DCs Inhibition of IL-18 activity and innate immunity
IL-38 17 kDa IL-1R1 with low affinity, IL-36R Basal epithelia of skin, spleen, fetal liver, placenta, and thymus and proliferating B cells of the tonsils Inhibition of the production of TH17 response cytokines; antagonism of IL-36
IFN-α, IFN-β Homodimer 15–21 kDa (IFN-α) and 22 kDa (IFN-β) IFNAR Mainly plasmacytoid DCs, but all nucleated cells can produce IFN-αβ in response to viral infection All cells express IFNAR in low numbers Defense against viral infection by orchestrating adaptive immune responses; stimulation of DC capability to present antigens; stimulation of macrophage antibody-dependent cytotoxicity; activation of naive T cells; promotion of development and proliferation of the B1 subset; trigger of apoptosis of tumor cells, as well as virus-infected cells
IFN-γ Homodimer 40-60 kDa IFNGR1/IFNGR2 NK and NKT cells, macrophages, myelomonocytic cells, TH1 cells, cytotoxic T lymphocytes, and B cells Epithelial cells, macrophages, DCs, NK cells, T and B cells Antiviral properties; promotion of cytotoxic activity and TH1 differentiation; upregulation of MHC class I and II; inhibition of cell growth; proapoptotic effects and control of activation-induced cell death; induction of epithelial apoptosis in skin and mucosa
TGF-β Homodimer 25 kDa TβR-I and TβR-II A large variety of cells, including epithelial cells, fibroblasts, and immune cells, such as eosinophils, macrophages, and Treg cells Epithelial and endothelial and mesenchymal and immune cells, including CD8 T cells, CD4 T cells, NK cells, monocytes, macrophages, neutrophils, and eosinophils Coordination of the proper development of the cardiac system and bone formation; induction of epithelial and endothelial to mesenchymal transition; balance of proinflammatory and anti-inflammatory effects by decreasing the cellular growth of almost all immune cell precursors; regulation of the differentiation of several TH cell subsets and induction of Treg cells; immune tolerance
TNF-α Homotrimer 26 kDa membrane-bound form + 17 kDa soluble form TNFR1 (p55/60, CD120a) and TNFR2 (p75/80, CD120b) Activated macrophages, monocytes, CD4+ T cells, B cells, neutrophils, NK cells and mast cells, fibroblasts, astrocytes, microglial cells, endothelial cells, smooth muscle cells, adipocytes, intrinsic renal cells, and others Nucleated cells Host defense; double role as a proinflammatory mediator by initiating a strong inflammatory response and an immunosuppressive mediator by limiting the extent and duration of inflammatory processes and by inhibiting the development of autoimmune diseases and tumorigenesis; epithelial apoptosis

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