Functional Specialization of Interleukin-17 Family Members

Iwakura, Yoichiro; Ishigame, Harumichi; Saijo, Shinobu; Nakae, Susumu

doi:10.1016/j.immuni.2011.02.012

Cited by 1,095 publications

(999 citation statements)

References 147 publications

Supporting

Mentioning

971

Contrasting

Unclassified

Order By: Relevance

“…63 However, their role in tumor pathogenesis and treatment remains controversial. 64,65 Recently, gemcitabine and 5-FU were shown to activate the inflammasome pathway in MDSCs, leading to IL-1b production, which, in turn, induced IL-17 secretion by CD4 T-cells and blunted the anticancer efficacy of chemotherapy. 66 In another report, however, optimal anticancer responses during doxorubicin treatment have been shown to require the IL-17-producing gd T-cell population.…”

Section: Box 1 Immune-based Effects Of Targeted Anticancer Compoundsmentioning

confidence: 99%

Immune-based mechanisms of cytotoxic chemotherapy: implications for the design of novel and rationale-based combined treatments against cancer

et al. 2013

View full text Add to dashboard Cite

Conventional anticancer chemotherapy has been historically thought to act through direct killing of tumor cells. This concept stems from the fact that cytotoxic drugs interfere with DNA synthesis and replication. Accumulating evidence, however, indicates that the antitumor activities of chemotherapy also rely on several off-target effects, especially directed to the host immune system, that cooperate for successful tumor eradication. Chemotherapeutic agents stimulate both the innate and adaptive arms of the immune system through several modalities: (i) by promoting specific rearrangements on dying tumor cells, which render them visible to the immune system; (ii) by influencing the homeostasis of the hematopoietic compartment through transient lymphodepletion followed by rebound replenishment of immune cell pools; (iii) by subverting tumor-induced immunosuppressive mechanisms and (iv) by exerting direct or indirect stimulatory effects on immune effectors. Among the indirect ways of immune cell stimulation, some cytotoxic drugs have been shown to induce an immunogenic type of cell death in tumor cells, resulting in the emission of specific signals that trigger phagocytosis of cell debris and promote the maturation of dendritic cells, ultimately resulting in the induction of potent antitumor responses. Here, we provide an extensive overview of the multiple immune-based mechanisms exploited by the most commonly employed cytotoxic drugs, with the final aim of identifying prerequisites for optimal combination with immunotherapy strategies for the development of more effective treatments against cancer.

show abstract

Section: Box 1 Immune-based Effects Of Targeted Anticancer Compoundsmentioning

confidence: 99%

Immune-based mechanisms of cytotoxic chemotherapy: implications for the design of novel and rationale-based combined treatments against cancer

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Interleukin‐17 plays protective roles against bacterial and fungal infection by recruiting neutrophils, activating T cells and inducing antimicrobial peptides and inflammatory cytokines 1, 4, 578 or Mycobacterium bovis BCG infection 79.…”

Section: γδ17 Cells In Pathogen Clearancementioning

confidence: 99%

“…Interleukin‐17A (IL‐17A, called ‘IL‐17’ hereafter) is a member of the IL‐17 family 1. The binding of IL‐17 to the heterodimeric receptor consisting of IL‐17RA and IL‐17RC subunits transduces signals to activate a group of cytokines and chemokines such as tumour necrosis factor, IL‐1, IL‐6, granulocyte colony‐stimulating factor, CXCL1 and CXCL2 through activation of the actin related gene 1‐TNF receptor associated factor 6–nuclear factor‐ κ B axis in the downstream 1.…”

Section: Introductionmentioning

confidence: 99%

“…The function of IL‐17 is pleiotropic. It plays a crucial role in the host defence against bacterial and fungal infection by inducing pro‐inflammatory cytokines and chemokines, recruiting neutrophils, and activating T cells and B cells 1, 2. Mice deficient for IL‐17RA are highly susceptible to Klebsiella pneumoniae 3 and IL‐17‐deficient mice are susceptible to bacterial and fungal infection 4, 5.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Interleukin‐17‐producing γδ T (γδ17) cells in inflammatory diseases

Akitsu

Iwakura

2018

Immunology

Self Cite

View full text Add to dashboard Cite

SummaryInterleukin‐17 (IL‐17) is a pro‐inflammatory cytokine and is involved in the development of many diseases. Recent studies have revealed that IL‐17‐producing γδ T cells (γδ17 cells) in addition to IL‐17‐producing CD4+ T cells [T helper type 17 (Th17) cells] are often the main producers of IL‐17 in mouse models of inflammatory diseases. γδ T cells are functionally committed during intra‐thymic differentiation. γδ thymocytes capable of producing IL‐17, which express the transcription factor retinoic‐acid‐receptor‐related orphan receptor γt and the signature cytokine receptor IL‐23R, leave the thymus, and produce IL‐17 rapidly by the stimulation with IL‐1β and IL‐23 in the periphery. Therefore, γδ17 cells play important roles in the early phase of host defence against pathogens and in inflammatory diseases. γδ T cells that can produce IL‐17 are also increased in the skin of patients with psoriasis and in peripheral blood of patients with ankylosing sclerosis. Indeed, the therapy targeting IL‐17 has been approved or is in clinical trials, and proved to be very efficient to treat psoriasis, psoriatic arthritis and ankylosing sclerosis. In this review, we discuss recent knowledge about the pathophysiological function of γδ17 cells in infection and inflammatory diseases and therapeutic advances targeting IL‐17.

show abstract

“…TRAF6 is recruited to the IL-17RA chain by the adaptor protein Act1, which binds directly to the SEFIR domain of IL-17RA [73]. Thus, Act1 and TRAF6 mediate downstream signaling of IL-17RA [74,75]. IL-17A induces several proinflammatory cytokines (IL-6, IL-1b, TNF, GM-CSF) and chemokines, in particular CCL20, which can attract CCR6 expressing Th17 cells in a positive feed forward loop, and ELR + (glutamic acid (E), leucin (L), arginine (R)) members of the CXC family of chemokines (CXCL1 and CXCL2) that are strong attractants for neutrophils [76,77].…”

Section: Il-17mentioning

confidence: 99%

Cytokines and effector T cell subsets causing autoimmune CNS disease

2011

View full text Add to dashboard Cite

a b s t r a c tAlthough experimental autoimmune encephalomyelitis (EAE) is limited in its potency to reproduce the entirety of clinical and histopathologic features of multiple sclerosis (MS), this model has been successfully used to prove that MS like autoimmunity in the CNS is orchestrated by autoantigen specific T cells. EAE was also very useful to refute the idea that IFN-c producing T helper type 1 (Th1) cells were the sole players within the pathogenic T cell response. Rather, ''new'' T cell lineages such as IL-17 producing Th17 cells or IL-9 producing Th9 cells have been first discovered in the context of EAE. Here, we will summarize new concepts of early and late T cell plasticity and the cytokine network that shapes T helper cell responses and lesion development in CNS specific autoimmunity.

show abstract

Functional Specialization of Interleukin-17 Family Members

Cited by 1,095 publications

References 147 publications

Immune-based mechanisms of cytotoxic chemotherapy: implications for the design of novel and rationale-based combined treatments against cancer

Immune-based mechanisms of cytotoxic chemotherapy: implications for the design of novel and rationale-based combined treatments against cancer

Interleukin‐17‐producing γδ T (γδ17) cells in inflammatory diseases

Cytokines and effector T cell subsets causing autoimmune CNS disease

Contact Info

Product

Resources

About