臨床検査54巻6号

2010年06月発行

記事購入ページに移動

今月の主題 注目されるサイトカイン 各論

アレルギーとサイトカイン

著者： 浅井友香里¹ 北島裕子¹ 井上博雅¹

所属機関： ¹九州大学大学院医学研究院呼吸器内科学

ページ範囲：P.630 - P.635

　アレルギー性炎症の病態には，IL-4，IL-5，IL-9，IL-13などのTh2(T helper 2)タイプのサイトカインが重要な役割を担っている．これらのサイトカインは，細胞膜上の受容体に結合し受容体が活性化すると，JAK/STAT系，Ras/ERK系などのシグナルが働くことにより応答遺伝子発現を変化させ作用が発現し，サイトカインシグナル抑制因子の発現も変化させる．最近，これら従来からのTh2サイトカインに加え，アレルギー性炎症におけるIL-18，新規Th2サイトカインIL-25，新規Th2関連サイトカインIL-33などの役割が注目されている．

参考文献

1) Wills-Karp M：Immunologic basis of antigen-induced airway hyperresponsiveness. Annu Rev Immunol　17：255-281, 1999

2) Yoshimura A, Naka T, Kubo M：Socs proteins, cytokine signalling and immune regulation. Nat Rev Immunol　7：454-465, 2007

3) Fukuyama S, Nakano T, Matsumoto T, et al：Pulmonary suppressor of cytokine signaling-1 induced by il-13 regulates allergic asthma phenotype. Am J Respir Crit Care Med　179：992-998, 2009

4) Jiang H, Chess L：Regulation of immune responses by t cells. N Engl J Med　354：1166-1176, 2006

5) Nurieva RI, Chung Y：Understanding the development and function of t follicular helper cells. Cell Mol Immunol 2010. [Epub ahead of print]

6) Chen Z, Tato CM, Muul L, et al：Distinct regulation of interleukin-17 in human t helper lymphocytes. Arthritis Rheum　56：2936-2946, 2007

7) Tanaka K, Ichiyama K, Hashimoto M, et al：Loss of suppressor of cytokine signaling 1 in helper t cells leads to defective th17 differentiation by enhancing antagonistic effects of ifn-gamma on stat3 and smads. J Immunol　180：3746-3756, 2008

8) Bullens DM, Truyen E, Coteur L, et al：Il-17 mrna in sputum of asthmatic patients：Linking t cell driven inflammation and granulocytic influx? Respir Res　7：135, 2006

9) Dragon S, Rahman MS, Yang J, et al：Il-17 enhances il-1beta-mediated cxcl-8 release from human airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol　292：L1023-L1029, 2007

10) Pichavant M, Goya S, Meyer EH, et al：Ozone exposure in a mouse model induces airway hyperreactivity that requires the presence of natural killer t cells and il-17. J Exp Med　205：385-393, 2008

11) Cheung PF, Wong CK, Lam CW：Molecular mechanisms of cytokine and chemokine release from eosinophils activated by il-17a, il-17f, and il-23：Implication for th17 lymphocytes-mediated allergic inflammation. J Immunol　180：5625-5635, 2008

12) Leech MD, Benson RA, De Vries A, et al：Resolution of der p1-induced allergic airway inflammation is dependent on cd4＋cd25＋foxp3＋ regulatory cells. J Immunol　179：7050-7058, 2007

13) Larche M：Regulatory t cells in allergy and asthma. Chest　132：1007-1014, 2007

14) Matsumoto K, Inoue H, Fukuyama S, et al：Frequency of foxp3＋cd4＋cd25＋t cells associates with the phenotypes of allergic asthma. Respirology　14：187-194, 2009

15) Okamura H, Tsutsi H, Komatsu T, et al：Cloning of a new cytokine that induces ifn-gamma production by t cells. Nature　378：88-91, 1995

16) Hoshino T, Wiltrout RH, Young HA：Il-18 is a potent coinducer of il-13 in nk and t cells：A new potential role for il-18 in modulating the immune response. J Immunol　162：5070-5077, 1999

17) Sugimoto T, Ishikawa Y, Yoshimoto T, et al：Interleukin 18 acts on memory t helper cells type 1 to induce airway inflammation and hyperresponsiveness in a naive host mouse. J Exp Med　199：535-545, 2004

18) Hata H, Yoshimoto T, Hayashi N, et al：Il-18 together with anti-cd3 antibody induces human th1 cells to produce th1-and th2-cytokines and il-8. Int Immunol　16：1733-1739, 2004

19) Hayashi N, Yoshimoto T, Izuhara K, et al：T helper 1 cells stimulated with ovalbumin and IL-18 induce airway hyperresponsiveness and lung fibrosis by IFN-gamma and IL-13 production. Proc Natl Acad Sci USA　104：14765-14770, 2007

20) Wild JS, Sigounas A, Sur N, et al：Ifn-gamma-inducing factor (il-18) increases allergic sensitization, serum ige, th2 cytokines, and airway eosinophilia in a mouse model of allergic asthma. J Immunol　164：2701-2710, 2000

. Immunity　15：985-995, 2001

22) Kawaguchi M, Kokubu F, Kuga H, et al：Modulation of bronchial epithelial cells by il-17. J Allergy Clin Immunol　108：804-809, 2001

23) Letuve S, Lajoie-Kadoch S, Audusseau S, et al：Il-17e upregulates the expression of proinflammatory cytokines in lung fibroblasts. J Allergy Clin Immunol　117：590-596, 2006

function of the novel cytokine il-25. J Immunol　169：443-453, 2002

25) Terashima A, Watarai H, Inoue S, et al：A novel subset of mouse nkt cells bearing the il-17 receptor b responds to il-25 and contributes to airway hyperreactivity. J Exp Med　205：2727-2733, 2008

26) Claudio E, Sonder SU, Saret S, et al：The adaptor protein ciks/act1 is essential for il-25-mediated allergic airway inflammation. J Immunol　182：1617-1630, 2009

27) Zaph C, Du Y, Saenz SA, et al：Commensal-dependent expression of il-25 regulates the il-23-il-17 axis in the intestine. J Exp Med　205：2191-2198, 2008

28) Schmitz J, Owyang A, Oldham E, et al：Il-33, an interleukin-1-like cytokine that signals via the il-1 receptor-related protein st2 and induces t helper type 2-associated cytokines. Immunity　23：479-490, 2005

29) Kondo Y, Yoshimoto T, Yasuda K, et al：Administration of il-33 induces airway hyperresponsiveness and goblet cell hyperplasia in the lungs in the absence of adaptive immune system. Int Immunol　20：791-800, 2008

30) Roussel L, Erard M, Cayrol C, et al：Molecular mimicry between il-33 and kshv for attachment to chromatin through the h2a-h2b acidic pocket. EMBO Rep　9：1006-1012, 2008

31) Luthi AU, Cullen SP, McNeela EA, et al：Suppression of interleukin-33 bioactivity through proteolysis by apoptotic caspases. Immunity　31：84-98, 2009

32) Chackerian AA, Oldham ER, Murphy EE, et al：Il-1 receptor accessory protein and st2 comprise the il-33 receptor complex. J Immunol　179：2551-2555, 2007

33) Pushparaj PN, Tay HK, H' Ng S C, et al：The cytokine interleukin-33 mediates anaphylactic shock. Proc Natl Acad Sci USA　106：9773-9778, 2009

34) Funakoshi-Tago M, Tago K, Hayakawa M, et al：Traf6 is a critical signal transducer in il-33 signaling pathway. Cell Signal　20：1679-1686, 2008

35) Iwahana H, Yanagisawa K, Ito-Kosaka A, et al：Different promoter usage and multiple transcription initiation sites of the interleukin-1 receptor-related human st2 gene in ut-7 and tm12 cells. Eur J Biochem　264：397-406, 1999

36) Hayakawa H, Hayakawa M, Kume A, et al：Soluble st2 blocks interleukin-33 signaling in allergic airway inflammation. J Biol Chem　282：26369-26380, 2007

37) Prefontaine D, Lajoie-Kadoch S, Foley S, et al：Increased expression of il-33 in severe asthma：Evidence of expression by airway smooth muscle cells. J Immunol　183：5094-5103, 2009

38) Kurowska-Stolarska M, Stolarski B, Kewin P, et al：Il-33 amplifies the polarization of alternatively activated macrophages that contribute to airway inflammation. J Immunol　183：6469-6477, 2009

39) Kurowska-Stolarska M, Kewin P, Murphy G, et al：Il-33 induces antigen-specific il-5＋t cells and promotes allergic-induced airway inflammation independent of il-4. J Immunol　181：4780-4790, 2008

40) Mangan NE, Dasvarma A, McKenzie AN, Fallon PG. T1/st2 expression on th2 cells negatively regulates allergic pulmonary inflammation. Eur J Immunol　37：1302-1312, 2007

41) Hoshino K, Kashiwamura S, Kuribayashi K, et al：The absence of interleukin 1 receptor-related t1/st2 does not affect t helper cell type 2 development and its effector function. J Exp Med　190：1541-1548, 1999

42) Kung TT, Stelts D, Zurcher JA, et al：Mast cells modulate allergic pulmonary eosinophilia in mice. Am J Respir Cell Mol Biol　12：404-409, 1995

43) Akbari O, Faul JL, Hoyte EG, et al：Cd4＋ invariant t-cell-receptor＋ natural killer t cells in bronchial asthma. N Engl J Med　354：1117-1129, 2006