PNAS：科学家揭示免疫系统IL-37分子的新角色

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来源：生物谷 2014-11-11 09:46; {* ~! V0 R7 K3 z: U" ?/ @3 t
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2014年11月11日 讯 /生物谷BIOON/ --近日，一篇发表在国际杂志PNAS上的研究论文中，来自美国科罗拉多大学癌症研究中心的研究人员通过研究描述了机体免疫系统通讯分子白细胞介素37（IL-37）的活性；该分子可以抑制炎性发展，而且当前研究发现IL-37可以抑制免疫系统识别并且靶标新抗原的能力。2 T1 X5 w0 E4 f4 V/ A) `5 H
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研究者Mayumi Fujita博士说道，揭示IL-37对机体免疫系统的效应或许可以帮助我们研究IL-37的功能及其和一系列疾病之间的关联；比如知道IL-37有助于创建机体总的免疫系统敏感性或许可以帮助控制IL-37的水平使得机体免疫系统致敏从而识别并且靶向作用肿瘤组织，或者在自身免疫疾病过程中使得免疫系统脱敏，比如风湿性关节炎等。- l( b$ d$ F3 O6 s
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IL-37是我们熟知的免疫系统中38种可以携带信息的白细胞介素类中的一种，当前研究显示，IL-37可以通过调节树突细胞来发挥作用，树突细胞在骨髓中形成可以迁移至机体其它部位同新型抗原相接触，比如迁移到皮肤或肠道内层中。5 m. I3 _. z" v/ Y6 j/ g
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这项研究中，研究人员发现IL-37可以促进半成熟的树突细胞形成，使其迁移至淋巴结中，但是这种树突细胞并不能以产生免疫反应的方式来提呈抗原，这就好比是IL-37可以在半成熟的状态下维持树突细胞的功能，而不是使其对新型抗原变得敏感。实际上本文研究中研究人员在携带IL-37的小鼠中揭示了一系列削减的免疫系统反应，包括CD40、IL-1b、IL-6和IL-12；其都参与了免疫反应的产生。1 O# R- Y, a* k. D

6 K& M% |4 x8 {4 `4 r研究者Fujita说道，IL-37或许是机体免疫系统调节的基本组分，而本文研究为我们理解基本的生物学机制来帮助理解众多疾病的发病原理也提供了一定的思路。（生物谷Bioon.com）0 K' W3 }" p3 R$ _' D, A
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- p  ~, g" V* Z" `% P1 c: N/ Odoi:10.1073/pnas.14167141116 \1 S, M; [0 Q9 u1 x
PMC:
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+ [8 F& T* H( s3 v% zSuppression of antigen-specific adaptive immunity by IL-37 via induction of tolerogenic dendritic cells
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& u; L  @! i6 B% nYuchun Luoa, Xiangna Caia,b, Sucai Liua, Sen Wanga,b, Claudia A. Nold-Petryc, Marcel F. Noldc, Philip Buflerd, David Norrisa,e, Charles A. Dinarellof,1, and Mayumi Fujitaa,e,1
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% h: r. t% J* lIL-1 family member IL-37 limits innate inflammation in models of colitis and LPS-induced shock, but a role in adaptive immunity remains unknown. Here, we studied mice expressing human IL-37b isoform (IL-37tg) subjected to skin contact hypersensitivity (CHS) to dinitrofluorobenzene. CHS challenge to the hapten was significantly decreased in IL-37tg mice compared with wild-type (WT) mice (−61%; P < 0.001 at 48 h). Skin dendritic cells (DCs) were present and migrated to lymph nodes after antigen uptake in IL-37tg mice. When hapten-sensitized DCs were adoptively transferred to WT mice, antigen challenge was greatly impaired in mice receiving DCs from IL-37tg mice compared with those receiving DCs from WT mice (−60%; P < 0.01 at 48 h). In DCs isolated from IL-37tg mice, LPS-induced increase of MHC II and costimulatory molecule CD40 was reduced by 51 and 31%, respectively. In these DCs, release of IL-1β, IL-6, and IL-12 was reduced whereas IL-10 secretion increased (37%). Consistent with these findings, DCs from IL-37tg mice exhibited a lower ability to stimulate syngeneic and allogeneic naive T cells as well as antigen-specific T cells and displayed enhanced induction of T regulatory (Treg) cells (86%; P < 0.001) in vitro. Histological analysis of CHS skin in mice receiving hapten-sensitized DCs from IL-37tg mice revealed a marked reduction in CD8+ T cells (−74%) but an increase in Treg cells (2.6-fold). Together, these findings reveal that DCs expressing IL-37 are tolerogenic, thereby impairing activation of effector T-cell responses and inducing Treg cells. IL-37 thus emerges as an inhibitor of adaptive immunity.