臨床整形外科43巻10号

2008年10月発行

境界領域／知っておきたい

インターロイキン（IL）-17

著者： 菊田順一¹ 佐伯行彦¹

所属機関： ¹独立行政法人国立病院機構大阪南医療センターリウマチ科・臨床研究部

ページ範囲：P.1016 - P.1020

■はじめに

　インターロイキン（IL）-17は1993年にクローニングされ，1995年に新しいサイトカインとして命名された．最近，IL-17を産生するCD4陽性ヘルパーT細胞の存在が明らかにされ，従来から知られているTh₁あるいはTh₂とよばれるサブセット以外の新たなサブセット（Th₁₇）であることが判明した．さらに，Th₁₇細胞は自己免疫疾患や感染防御などにおいて鍵となる役割を果たしていることが報告され，非常に注目されている．今回，炎症性自己免疫疾患や感染症におけるIL-17の役割について概説したい．

参考文献

1）Aggarwal S, Gurney AL：IL-17：prototype member of an emerging cytokine family. J Leukoc Biol 71：1-8, 2002

2）Billiau A, Hermans H, Vandekerckhove F, et al：Enhanced of experimental allergic encephalomyelitis in mice by antibodies against IFN-γ. J Immunol 140：1506-1510, 1988

3）Chabaud M, Durand JM, Buchs N, et al：Human interleukin-17：a T cell-derived proinflammatory cytokine produced by rheumatoid synovium. Arthritis Rheum 42：963-970, 1999

4）Chabaud M, Lubbers E, Joosten L, et al：IL-17 derived from juxta-articular bone and synovium contributes to joint degradation in rheumatoid arthritis. Arthritis Res 3：168-177, 2001

5）Cua DJ, Sherlock J, Chen Y, et al：Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature 421：744-748, 2003

6）Ferber IA, Brocke S, Taylor-Edwards C, et al：Mice with a disrupted interferon-γ gene are susceptible to the induction of experimental autoimmune encephalomyelitis（EAE）. J Immunol 156：5-7, 1996

7）Happel KI, Dubin PJ, Zheng M, et al：Divergent roles of IL-23 and IL-12 in host defense against Klebsiella pneumoniae. J Exp Med 202：761-769, 2005

8）Harrington LE, Hatton RD, Mangan PR, et al：Interleukin-17 producing CD4＋effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol 6：1123-1132, 2005

9）Infante-Duarte C, Horton HF, Byrne MC, et al：Microbial lipopeptides induce the production of IL-17 in Th cells. J Immunol 165：6107-6115, 2000

10）Ivanov, II, McKenzie BS, Zhou L, et al：The orphan nuclear receptor RORγt directs the differentiation program of proinflammatory IL-17＋T helper cells. Cell 126：1121-1133, 2006

11）Jacob CO, Holoshitz J, Van der Meide P, et al：Heterogeneous effects of Interferon-γ in adjuvant-induced arthritis. J Immunol 142：1500-1505, 1989

12）Kolls JK, Linden A：Interleukin-17 family members and inflammation. Immunity 21：467-476, 2004

13）Lubberts E, Joosten LA, van de Loo FA, et al：Overexpression of IL-17 in the knee joint of collagen type Ⅱ immunized mice promotes collagen arthritis and aggravates joint destruction. Inflamm Res 51：102-104, 2001

14）Mangan PR, Harrington LE, O'Quinn DB, et al：Transforming growth factor-β induces development of the TH17 lineage. Nature 441：231-234, 2006

15）Moseley TA, Haudenschild DR, Rose L, et al：Interleukin-17 family and IL-17 receptors. Cytokine Growth Factor Rev 14：155-174, 2003

16）Mosmann TR, Coffman RL：Th1 and Th2 cells：different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol 7：145-173, 1989

17）Nakae S, Nambu A, Sudo K, et al：Suppression of immune induction of collagen-induced arthritis in IL-17-deficient mice. J Immunol 171：6173-6177, 2003

18）Nakajima H, Takamori H, Hiyama Y, et al：The effect of treatment with recombinant gamma-interferon on adjuvant-induced arthritis in rat. Agents Actions 34：63-65, 1991

19）Page G, Miossec P：Rank and RANKL expression as markers of dendritic cell-T cell interactions in paired samples of rheumatoid synovium and lymph nodes. Arthritis Rheum 52：2307-2312, 2005

20）Park H, Li Z, Yang XO, et al：A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol 6：1133-1141, 2005

21）Rouvier E, Luciani MF, Mattei MG, et al：CTLA-8, cloned from an activated T cell, bearing AU-rich messenger RNA instability sequences, and homologous to a herpesvirus saimiri gene. J Immunol 150：5445-5456, 1993

22）Sato K, Suematsu A, Okamoto K, et al：Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction. J Exp Med 203：2673-2682, 2006

23）Veldhoen M, Hocking RJ, Atkins CJ, et al：TGFβ in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17 producing T cells. Immunity 24：179-189, 2006

24）Yao Z, Fanslow WC, Seldin MF, et al：Herpesvirus Saimiri encodes a new cytokine, IL-17, which binds to a novel cytokine receptor. Immunity 3：811-821, 1995