Daftar Lengkap Sitokin 1-38 dan Berbagai Fungsinya

August 3, 2021August 3, 2021 DOKTER INDONESIA ONLINE

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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 T_H17 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	T_H2 cells, basophils, eosinophils, mast cells, NKT cells and γ/δ T cells	T and B cells	Induction of T_H2 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	T_H2 cells, activated eosinophils and masts cells, T_C2 cells, γδ T cells, NK and NK T cells and CD4⁻c-Kit⁻CD3ε⁻IL2Rα⁻ (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	T_H2, T_H9, T_H17, 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 T_H1- 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 (T^H1 cells), NK cells	Development and maintenance of T_H1 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 T_H2 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)	T_H17 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)	T_H17 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 T_H1 or T_H2 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 T_H2 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 T_H17 and T_H9), 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 T_H17 and T_H22 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 (T_H17 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	T_H2 cells, mast and epithelial cells, eosinophils, and basophils from atopic subjects	T_H2 memory cells, fibroblasts, basophils, NKT cells, macrophages, and ILC2s	Induction of T_H2 responses and inhibition of both T_H1 and T_H17 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 T_H17 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 T_H1 cell differentiation; inhibition of T_H17 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 T_H2 response and upregulation of T_H1 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 T_H2) 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 T_H2-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 T_H1 and T_H2 cells; very low levels on T_H17 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 T_H17 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, T_H1 cells, cytotoxic T lymphocytes, and B cells	Epithelial cells, macrophages, DCs, NK cells, T and B cells	Antiviral properties; promotion of cytotoxic activity and T_H1 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 T_H 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