白细胞介素17及其在寄生虫学上的研究新进展

Research advances in Interleukin-17 and its application in parasitology

白细胞介素17(Interleukin 17,IL-17)是一种多家族成员的细胞因子,包括IL-17A～F,受体有5种(IL-17RA～IL-17RE)。与IL-1、TNF-α信号传导途径类似,IL-17受RORγt调节,能激活NF-κB、MAP激酶和ERK1/2等信号分子,发挥其生物学功能。IL-17家族具有强大的致炎作用,能促进中性粒细胞增多且向局部组织浸润;可促进多细胞因子释放,积极参与机体体液免疫和细胞免疫,以及造血作用和家族成员间协同作用。IL-17虽在适应型免疫反应过程中产生,但其经典功能却主要在固有免疫调节反应中发挥,且与寄生虫对宿主的侵袭和致病关系紧密,在宿主抗寄生虫感染过程中起重要作用。因此,本文就IL-17及其在寄生虫学上的研究做一综述。

Interleukin 17 is a family of cytokines consisted of IL-17A,IL-17B,IL-17C,IL-17D,IL-17E and IL-17F.IL-17 has been designated IL-17A,which secreted exclusively by activated T-cells.Currently,the cognate receptors for the IL-17 family identified thus far are： IL-17R,IL-17RH1,IL-17RL（receptor like）,IL-17RD and IL-17RE.Therefore,these different members of the family are characteristic of various biological functions.IL-17A is an important cytokine that induces inflammatory responses through the organized production of inflammatory cytokines and induces neutrophil migration.And IL-17B may be related with digestive function of the body.Directly or indirectly,IL-17C participates in the process of immune response and inflammation reaction,and is able to promote mononuclear cells to secrete more cytokines,like TNF-α,IL-1β.IL-17D is expressed in skeletal muscle,lung,adipose tissue,heart,pancreas and brain.In colony formation assays,rIL-17D has an inhibitory effect on hemopoiesis of myeloid progenitor cells.As the newest member of the IL-17 cytokine family,IL-17E is the most distant from IL-17A.IL-17E can initiate,promote and augment Th2 cell-mediated immune responses,herein playing a pivotal role in allergic disease and defense against parasites.The similar characteristics between IL-17F and IL-17A contribute to the higher amino acid sequence homology,44%.Therefore,the biological characteristics of IL-17 family are extremely complicated,such as inducing neutrophil migration,initiating and promoting inflammation reactions,augmenting the production of cytokines,and hematopoiesis.As potentially dangerous pathogens,parasitic diseases seriously threaten public health and social security.Recent studies have shown that IL-17 family,especially IL-17A,may maintain the close relationships with invasiveness and pathogenicity of parasites,and play a key role in the biological functions that hosts defense against parasitic infection.In a proinflammatory cytokine environment,like IL-17,the infection with Schistosoma mansoni leads to hepatic egg-induced granulomatous inflammation.Interestingly,Trichinella spiralis larva intestinal invasion can induce the production of Th2 and Th17 cell-related cytokines while higher IL-17 is associated with lower incidence of malaria.In the absence of IL-17A,the efficient activation of immune-related cells critical for the killing of Trypanosoma cruzi was impaired,leading to the greater susceptibility of the mice to T.cruzi infection.Consequently,we can consider that IL-17A is crucial in the resolution of T.cruzi infection.However,the regulatory mechanisms are still unclear.So the researches that lucubrate the relation between IL-17 family and parasitic infections are vital and significant on development of new type vaccines and on prevention of parasites.