技術情報
サイトカインとその主な機能
■インターキロン
■腫瘍壊死因子 (TNF) スーパーファミリー
■腫瘍増殖因子 (TGF) β スーパーファミリー
■インターフェロン (IFN)
■コロニー刺激因子 (CSF)
| サイトカイン | 産生細胞 | 標的細胞 | 主な機能 |
| インターキロン | |||
| IL-1α, IL-1β | Macrophages, B cells, DCs | B cells, NK cells, T cells | 炎症促進、増殖と分化、骨髄細胞の増殖 |
| IL-1RA | IL-1 を介する抗炎症 | ||
| IL-2 | T cells | Activated T and B cells, NK cells | 増殖と活性化 |
| IL-3 | T cells, NK cells | Stem cells | 造血前駆細胞の増殖と分化 |
| IL-4 | Th cells | B cells, T cells, macrophages | B細胞および細胞傷害性 T細胞の増殖、MHC クラス II 発現を促進、IgG および IgE 産生を誘導 |
| IL-5 | Th cells | Eosinophils, B cells | 増殖と成熟、IgA および IgM 産生を誘導 |
| IL-6 | Th cells, macrophages, fibroblasts | Activated B cells, plasma cells | 形質細胞への分化、IgG を産生 |
| IL-7 | BM stromal cells, epithelial cells | Stem cells | B細胞 および T細胞の増殖因子 |
| IL-8 | Macrophages | Neutrophils | 走化性を誘導、炎症促進 |
| IL-9 | T cells | T cells | 成長と増殖 |
| IL-10 | T cells | B cells, macrophages | サイトカインの産生と単核細胞の機能を阻害、抗炎症 |
| IL-11 | BM stromal cells | B cells | 分化、急性期タンパク質を誘導 |
| IL-12 | T cells | NK cells | NK細胞の活性化 |
| IL-13 | Th cells, mast cells, NK cells | B cells, macrophages | B細胞の成長と分化を誘導、Th1細胞を阻害 |
| IL-14 | T cells, B cells | B cells | B細胞の成長と分化、Ig 分泌を阻害 |
| IL-15 | Macrophages, DCs, fibroblasts | T cells, NK cells | 増殖と活性化 |
| IL-16 | T cells, eosinophils | CD4+ T cells | CD4+ T細胞のリクルート |
| IL-17A | Th17 cells, NK cells, NKT cells | Neutrophils, fibroblast, epithelial cells | 炎症促進、T細胞の増殖 |
| IL-17B,C,D | Neuronal cells, epithelial cells, B and T cells | Monocytes, endothelial cells, epithelial cells | 抗菌、炎症促進 |
| IL-17F | Th17 cell, NK cells, NKT cells, T cells | Epithelial cells, endothelial cells, lymphocytes | 炎症促進、好中球のリクルートおよび活性化 |
| IL-18 | Monocytes, DCs | T cells, NK cells, macrophages, epithelial cells | 炎症促進、NK細胞の細胞毒性を増強、T細胞の分化 |
| IL-19 | Monocytes | Keratinocytes | 炎症促進 |
| IL-20 | Monocytes, Keratinocytes | Keratinocytes | ケラチノサイトの増殖と分化 |
| IL-21 | T cells, NKT cells | Lymphocytes, DCs | T細胞の増殖、B細胞の分化を促進、NK細胞の細胞毒性を増強 |
| IL-22 | Th17 cells | Fibroblasts, epithelial cells | 病原体からの防御、創傷の治癒、組織の再構成 |
| IL-23 | Macrophages, DCs | Lymphocytes | 炎症促進、T細胞増殖を促進、NK細胞の活性化 |
| IL-24 | Melanocytes, keratinocytes, monocytes, T cells | Cancer cells | 腫瘍を抑制、創傷の治癒 |
| IL-25 (IL-17E) | T cells, mast cells, epithelial cells | T cells, fibroblasts, NKT cells, macrophages | Th2細胞の分化と増殖を促進 |
| IL-26 | T cells, NK cells | Epithelial cells | 上皮細胞の活性化と制御 |
| IL-27 | DCs, macrophages, epithelial cells | T cells, NK cells | Th1細胞の分化を促進、Th17細胞の応答を阻害 |
| IL-28A/B | DCs | Monocytes, DCs, CD4+ T cells | Th2細胞の応答の下方制御と Th1細胞の応答の上方制御 |
| IL-29 | |||
| IL-30 | Monocytes | Lymphocytes, mast cells, endothelial cells | サイトカイン誘発性肝障害の予防と治療 |
| IL-31 | T cells, monocytes, macrophages, DCs, | Keratinocytes, epithelial cells | 炎症促進 |
| IL-32 | Monocytes, macrophages, NK cells, T cells, epithelial cells | Macrophages, DCs, T cells, PBMCs, monocytes | 炎症促進 |
| IL-33 | Mast cells, Th2 cells | DCs, T cells, B cells | Th2細胞の応答を誘導 |
| IL-34 | Phagocytes, epithelial cells | Monocytes, macrophages | 骨髄細胞系列の分化を調節、ミクログリアの増殖 |
| IL-35 | Treg cells, monocytes, endothelial cells, epithelial cells | NK cells, T cells | 免疫抑制 |
| IL-36 | Endothelial cells | Keratinocytes, DCs, T cells | 炎症促進 |
| IL-37 | Monocytes, Cancer cells | DCs | 自然免疫の調節、炎症促進 |
| IL-38 | Epithelial cells | T cells | Th17細胞の応答を阻害 |
| IL-39 | B cells | Neutrophils | 分化と増殖の誘導 |
| IL-40 | BM cells, B cells | unknown | 体液性免疫応答の誘発 |
| 腫瘍壊死因子 (TNF) スーパーファミリー | |||
| TNF-α | Macrophages, NK cells, T cells, B cells | Neutrophils, macrophages, monocytes, endothelial cells | 免疫細胞の調節、炎症、アポトーシス、腫瘍形成とウイルス複製を阻害 |
| TNF-β | T cells, B cells | Many cell types | 炎症促進、抗ウイルス応答、二次リンパ器官の発達、腫瘍形成 |
| TNF-γ | T cells, B cells | Myeloid cells, other cell types | 炎症促進、抗ウイルス応答、二次リンパ器官の発達、腫瘍形成 |
| OX40L | T cells, B cells, DCs, monocytes | T cells, B cells, DCs | T細胞の免疫応答の活性化 |
| CD40L | T cells, B cells, DCs, monocytes | B cells, APCs | 適応免疫応答の調節 |
| FasL | T cells, B cells, NK cells | APCs, many other cell types | T細胞の恒常性の調節 |
| CD27L | T cells, B cells, DCs, monocytes | T cells, B cells | B細胞の活性化とT細胞の恒常性の調節 |
| CD30L | Neutrophils, B cells, macrophages, T cells | T cells, B cells, DCs | T細胞およびB細胞のアポトーシスを誘導、自己免疫の予防 |
| 4-1BBL | T cell, B cells, DCs, monocytes, macrophages | T cells, B cells, DCs | 単球の活性化と遊走を促進 |
| TRAIL | NK cells, T cells | Many cell types | 腫瘍形成を阻害、アポトーシスを誘導 |
| RANKL | T cells, Osteoprotegerin | Osteoclasts, many cell types | 組織の成長、樹状細胞（DCs）の成熟 |
| TWEAK | Monocytes, macrophages, endothelial cells | Tissue progenitors, epithelial cells, endothelial cells | 血管新生を調節、アポトーシスを誘導 |
| APRIL | Macrophages, DCs | B cells | B細胞の発生と形質細胞の生存を調節 |
| BAFF | Macrophages, DCs, astrocytes | B cells | B細胞の増殖と分化を誘導 |
| LIGHT | T cells, monocytes, DCs | B cells, NK cells, DCs, other tissue | T細胞増殖を誘導、アポトーシスを調節 |
| TL1A | Macrophages, endothelial cells | T cells | 血管新生を阻害 |
| GITRL | DCs, macrophages, B cells | Treg cells, T cells | T細胞の生存を調節 |
| 腫瘍増殖因子 (TGF) β スーパーファミリー | |||
| TGF-βs; TGF-β1, β2, β3 | Epithelial cells, fibroblasts, eosinophils, macrophages, T cells | Various | 炎症促進と抗炎症のバランスを調節、Th細胞サブセットの分化、Treg 維持を誘導、上皮間葉転換 |
| Activins/Inhibins | Monocytes, macrophages | T cells, macrophages, microglial cells, DCs, mast cells, B cells | 月経周期の調節、代謝、止血、免疫反応、傷の修復 |
| BMPs/GDFs | Thymic stromal cells, cardiomyocytes, macrophages | Monocytes, fibroblasts, cardiomyocytes | 胎児および胚の発達、軟骨の発達、脂質生成、線維化促進、抗肥大、心筋細胞の生存促進、免疫応答 |
| インターフェロン (IFN) | |||
| IFN-α | Leukocytes | Various | 抗ウイルス、NK細胞とT細胞の活性化を促進、巨核球幹細胞の分化と増殖を阻害 |
| IFN-β | Fibroblasts | Various | 抗ウイルス、NK 細胞および T 細胞上の MHC-I の発現を促進、炎症抑制 |
| IFN-γ | Th1 cells, NK cells | Various | 抗ウイルス、マクロファージの活性化、好中球と単球の機能を増強、 細胞上の MHC-I および MHC-II の発現を増加 |
| コロニー刺激因子 (CSF) | |||
| G-CSF | Fibroblasts, endothelium | Stem cells in BM | 顆粒球の生成 |
| GM-CSF | T cells, macrophages, fibroblasts | Stem cells | 顆粒球、単球、好酸球の生成 |
| M-CSF | Fibroblast, endothelium | Stem cells | 単球の生成と活性化 |
| Erythropoietin | Endothelium | Stem cells | 赤血球の生成 |
略語: BM, bone marrow; DCs, dendritic cells; NK cell, natural killer cell; G-CSF, granulocyte-colony stimulating factor; M-CSF, macrophage-colony stimulating factor; Th, T helper cell; Treg, regulatory T cell.
サイトカインファミリー
| ファミリー | メンバー | ||
| Hematopoietic | |||
| - Common γ chain | IL-2, IL-4, IL-7, IL-9, IL-15, IL-21 | ||
| - Shared β chain (CD131) | IL-3, IL-5, GM-CSF | ||
| - Shared IL-2β chain (CD122) | IL-2, IL-15 | ||
| - Other hematopoietic | IFN-γ, IL-7, IL-13, IL-21, IL-31, TSLP | ||
| IL-1 family | IL-1α, IL-1β, IL-1RA, IL-18, IL-33, IL-36, IL-37 | ||
| IL-6 family | IL-6, IL-11, IL-27, IL-31, CNTF, CT-1, LIF, OSM, OPN | ||
| IL-12 family | IL-12, IL-23, IL-27, IL-35 | ||
| IL-10 superfamily | IL-10, IL-19, IL-20, IL-22, IL-24, IL-26, IL-28, IL-29 | ||
| IL-17 family | IL-17A-F, IL-25 (IL-17E) | ||
| Interferons | |||
| - Type I interferons | IFN-α, IFN-β, IFN-ω | ||
| - Type II interferons | IFN-γ (also a hematopoietic cytokine) | ||
| - Type III interferons | IFN-λ1 (IL-29), IFN-λ2 (IL-28A), IFN-λ3 (IL-28B) | ||
| TNF superfamily | TNF-α, TNF-β, BAFF, APRIL | ||
略語: GM-CSF, granulocyte-macrophage-colony stimulating factor; IFN, interferon; TSLP, thymic stromal lymphopoietin.; CNTF, ciliary neurotrophic factor; CT-1, ardiotrophin-1; LIF, leukemia inhibitory factor; OSM, oncostatin M; OPN, osteopontin; TNF, tumor necrosis factor.
参考文献
- Dinarello CA. Historical insights into cytokines. Eur J Immunol. 2007 Nov;37 Suppl 1:S34-45.
- Turner MD, et al. Cytokines and chemokines: At the crossroads of cell signalling and inflammatory disease. Biochim Biophys Acta. 2014 Nov;1843(11):2563-2582.
- Commins SP, et al. Immunologic messenger molecules: cytokine, interferons, and chemokines. J Allergy Clin Immunol. 2010 Feb;125(2 Suppl 2):S53-72.
- Akdis M, et al. Interleukins (from IL-1 to IL-38), interferons, transforming growth factor β, and TNF-α: Receptors, functions, and roles in diseases. J Allergy Clin Immunol. 2016 Oct;138(4):984-1010.
- Justiz Vaillant AA, et al. Interleukin. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. [Internet] Available at https://www.ncbi.nlm.nih.gov/books/NBK499840/ [Accessed 17th April 2020]
- Tumor necrosis factor superfamily. [Internet] Available at https://en.wikipedia.org/wiki/Tumor_necrosis_factor_superfamily [Accessed 17th April 2020]
- Chen W, et al. Immunoregulation by members of the TGFβ superfamily. Nat Rev Immunol. 2016 Nov 25;16(12):723-740.
- Anis Hanna, et al. The Role of the TGF-β Superfamily in Myocardial Infarction. Front Cardiovasc Med. 2019; 6: 140. Published online 2019 Sep 18
- Zhu J, et al. CD4 T cells: fates, functions, and faults. Blood. 2008 Sep 1;112(5):1557-69.
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