Article

Functional Specialization of Interleukin-17 Family Members

Laboratory of Molecular Pathogenesis, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, Japan.
Immunity (Impact Factor: 21.56). 02/2011; 34(2):149-62. DOI: 10.1016/j.immuni.2011.02.012
Source: PubMed

ABSTRACT

Interleukin-17A (IL-17A) is the signature cytokine of the recently identified T helper 17 (Th17) cell subset. IL-17 has six family members (IL-17A to IL-17F). Although IL-17A and IL-17F share the highest amino acid sequence homology, they perform distinct functions; IL-17A is involved in the development of autoimmunity, inflammation, and tumors, and also plays important roles in the host defenses against bacterial and fungal infections, whereas IL-17F is mainly involved in mucosal host defense mechanisms. IL-17E (IL-25) is an amplifier of Th2 immune responses. The functions of IL-17B, IL-17C, and IL-17D remain largely elusive. In this review, we describe the identified functions of each IL-17 family member and discuss the potential of these molecules as therapeutic targets.

Download full-text

Full-text

Available from: Yoichiro Iwakura
  • Source
    • "IL-17A and IL-17F secreted by Th17 subset are 2 highly homologous pro-inflammatory cytokines and belong to IL-17 family which consists of six subtypes: IL-17A, IL-17B, IL-17C, IL-17D, IL17E and IL-17F[16]. Since their high degree of homology, IL-17A and IL-17F bind the same receptor complex which is comprised of IL-17RA and IL-17RC and consequently exhibits similar biological activities in many aspects[17,18]. Both IL-17A and IL-17F can form disulfide-bonded IL-17AA, IL-17FF homodimers and IL-17AF heterodimer. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Non-Hodgkin’s lymphomas (NHLs) are a heterogeneous group of neoplasm in which 90% are B-cell lymphomas and 10% T-cell lymphomas. Although T-helper 17 (Th17) cells have been implicated to be essential in the pathogenesis of autoimmune and inflammatory diseases, its role in B-cell non-Hodgkin’s lymphoma (B-NHL) remains unknown. In this study, we observed a significantly decreased frequency of Th17 cells in peripheral blood from B-NHL patients compared with healthy individuals, accompanied with increased Th1 cells. IL-17AF plasma levels were remarkably decreased in B-NHL patients, accompanied with undetectable IL-17FF and unchangeable IL-17AA. Moreover, Th17 and Th1 cells became normalized after one or two cycles of chemotherapy. Interestingly, in B-NHL, circulating Th17 cells frequencies were significantly higher in relapsed patients than those in untreated patients or normal individuals. Meanwhile, there was no statistical difference regarding the frequencies of Th1 cells between relapsed and untreated patients. Taken these data together, circulating Th17 subset immune response may be associated with the response of patients to treatment and with different stages of disease.
    Full-text · Article · Jan 2016 · PLoS ONE
  • Source
    • "Among them, IL-17A and IL-17F share the highest sequence homology and have similar biological functions. Both bind to IL-17RA and IL-17RC chains [1]. IL-17 is primarily secreted by T helper (Th) 17 cells and innate lymphocytes (í µí»¾í µí»¿ T cells, natural killer (NK) cells, and innate lymphoid cells) [2]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Metastatic disease accounts for more than 90% of deaths from breast cancer. Yet the factors that trigger metastasis, often years after primary tumor removal, are not understood well. Recently the proinflammatory cytokine interleukin- (IL-) 17 family has been associated with poor prognosis in breast cancer. Here we review current literature on the pathogenic mechanisms driven by IL-17 during breast cancer progression and connect these findings to metastasis. These include (1) direct effects of IL-17 on tumor cells promoting tumor cell survival and invasiveness, (2) regulation of tumor angiogenesis, and (3) interaction with myeloid derived suppressor cells (MDSCs) to inhibit antitumor immune response and collaborate at the distant metastatic site. Furthermore, IL-17 might also be a culprit in bone destruction caused by late stage bone metastasis. Interestingly, in addition to these potential prometastasis functions, there is also evidence for an opposite, antitumor role of IL-17 during cancer therapies. We hypothesize that these contradictory roles may be due to chronic, imbalanced versus acute transient nature of the immune reactions, as well as differences in the cells that interact with IL-17 + cells under different circumstances.
    Full-text · Article · Dec 2015 · Mediators of Inflammation
  • Source
    • "IL-17 is the dominant pro-inflammatory cytokine produced by Th17 cells. It has pleiotropic effects such as inducing the release of other cytokines that lead to proinflammatory processes and neutrophil-mobilization [3]. IL-23 and IL-17 have been implicated in the pathogenesis of many autoimmune diseases, such as inflammatory bowel diseases, psoriatic arthritis, and spondyloarthritis [4e6]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: This study investigated the effects of interleukin 23 (IL-23) on the production of cytokines (IL-1, IL-4, IL-10, and IL-17), the differentiation of Treg/Th17 and STAT3 (i.e., signal transducer and activator of transcription 3) in human decidual immune cells (DICs) during early pregnancy. Methods: DICs were treated with recombinant human IL-23 and an antibody against IL-23 subunit p19. The differentiation of Treg and Th17 cells was detected by flow cytometry. Levels of IL-23 receptor (IL-23R), STAT3, and phosphorylated STAT3 (pSTAT3) was examined by Western blot. The production of IL1, IL4, IL10, and IL-17 in DICs was measured by ELISA. Results: Exogenous recombinant human IL-23 significantly promoted the differentiation of Th17 cells from DICs, while anti-IL-23 antibody significantly promoted the differentiation of Treg cells from DICs. Consistent with the differentiation of Th17 and Tregs cells, levels of IL-1β and IL-17 correlated positively with IL-23 treatment, and anti-IL-23 antibody increased the secretion of IL-4 and IL-10 from DICs. Levels of pSTAT3, but not STAT3 or IL-23R, were significantly elevated by recombinant IL-23 treatment; anti-IL-23 antibody significantly decreased the levels of pSTAT3 and IL-23R in DICs. Conclusions: IL-23 mediates the differentiation of Th17 and Treg cells and the production of associated cytokines in DICs. The potential mechanism likely involves the STAT3 pathway.
    Full-text · Article · Nov 2015 · Biochemical and Biophysical Research Communications
Show more