Suppression of Immune Induction of Collagen-Induced Arthritis in IL-17-Deficient Mice

Nakae, Susumu; Nambu, Aya; Sudo, Katsuko; Iwakura, Yoichiro

doi:10.4049/jimmunol.171.11.6173

Cited by 1,162 publications

(976 citation statements)

References 28 publications

Supporting

Mentioning

919

Contrasting

Unclassified

Order By: Relevance

“…It was later reported that the role of IL-23 involved induction or expansion of Th17 cells; autoantigen-specific Th17 cells transferred EAE to naïve mice [22]. Furthermore, mice treated with anti-IL-17 neutralizing antibody [75] or IL-17 À/À mice [76,77] had reduced susceptibility to experimentally induced autoimmunity, though the attenuation was not as pronounced as that observed in IL-23 À/À mice. This was complemented by studies in humans, which showed that CD4 1 T cells from MS patients secrete higher levels of IL-17 than healthy donors following in vitro stimulation with plate-bound anti-CD3 [78].…”

Section: Role Of Il-17-secreting T Cells In Immune-mediated Diseasesmentioning

confidence: 97%

Induction, function and regulation of IL‐17‐producing T cells

2008

View full text Add to dashboard Cite

Recent reports have provided convincing evidence that IL-17-producing T cells play a key role in the pathogenesis of organ-specific autoimmune diseases, a function previously attributed exclusively to IFN-c-secreting Th1 cells. Furthermore, it appears that IL-17-producing T cells can also function with Th1 cells to mediate protective immunity to pathogens. Although much of the focus has been on IL-17-secreting CD4 1 T cells, termed The main function of IL-17-secreting T cells is to mediate inflammation, by stimulating production of inflammatory cytokines, such as TNF-a, IL-1b and IL-6, and inflammatory chemokines that promote the recruitment of neutrophils and macrophages.Key words: Autoimmunity . IL-17 . Infection . Inflammation IntroductionMore than 20 years ago Mosmann and Coffman reported that distinct CD4 1 T-cell subtypes, termed Th1 and Th2 cells, could be distinguished on the basis of cytokine secretion and function [1]. The Th1-Th2 model provided a useful but simplistic basis for our understanding of the mechanisms of immunity to infection and also attempted to explain the role of T cells in the pathogenesis of autoimmunity and allergy/asthma. The original hypothesis was that IFN-g-secreting CD4 1 cells mediated protective immunity to intracellular pathogens by promoting macrophage activation and stimulating production of complement fixing and virus neutralizing antibodies, but also promoted inflammatory responses and mediated the pathology in certain autoimmune diseases. In contrast, CD4 1 T cells that secreted IL-4, IL-5, IL-10 and IL-13 were considered to be the main helper T cells providing help for B-cell production of antibody, especially IgG1 in mice, and mediated protective immunity to extracellular pathogens. These Th2 cells were also anti-inflammatory, controlling Th1 responses, but at the same time mediated allergic reactions and had an inflammatory and pathological role in asthma.The identification of additional T-cell subtypes has led to a shift in the Th1-Th2 paradigm and has helped to explain some anomalies in the original model. In the mid 1990s suppressor T cells were re-discovered as Treg cells and were shown to have a major role in controlling immune responses to self-antigens, thereby preventing autoimmunity. Furthermore, these cells rather than the reciprocal Th1 or Th2 populations were shown to be the major regulator of effector T cells, functioning to maintain self-tolerance, prevent autoimmunity and limit collateral damage during immune responses to pathogens [2,3].There were a number of other observations which could not be explained on the basis of the two Th1 and Th2 subtypes. Mini-ReviewDespite the assumption that Th1 cells mediated autoimmunity, mice deficient in IFN-g or IFN-g receptors were found to have increased susceptibility to EAE and collagen-induced arthritis (CIA) [4,5]. Furthermore, EAE was exacerbated in mice deficient in the Th1 polarizing cytokine, 7]. It was then discovered that mice deficient in the novel IL-12 family member, IL-23 were resistant to EAE [6]....

show abstract

Section: Role Of Il-17-secreting T Cells In Immune-mediated Diseasesmentioning

confidence: 97%

Induction, function and regulation of IL‐17‐producing T cells

2008

View full text Add to dashboard Cite

show abstract

“…Il17 –/– mice show significantly reduced severity in various inflammatory and autoimmune disease models, such as collagen‐induced arthritis,6 Il1rn −/− mouse arthritis,7 EAE8 and imiquimod (IMQ)‐induced skin inflammation,9, 10 suggesting critical roles of IL‐17 in inflammatory/autoimmune diseases. γδ 17 cells are detected in inflamed tissues of these disease models.…”

Section: The Pathogenic Roles Of γδ17 Cells In Mouse Inflammatory Dismentioning

confidence: 99%

“…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. Interleukin‐17 is also implicated in various inflammatory/autoimmune disease models such as experimental autoimmune encephalomyelitis (EAE), arthritis in IL‐1 receptor antagonist‐deficient (Il1rn –/– ) mice and imiquimod‐induced psoriatic dermatitis in mice 6, 7, 8, 9, 10. Anti‐IL‐17 and anti‐IL‐17RA antibodies are effective to treat patients with psoriasis and psoriatic arthritis 11, 12, 13.…”

Section: Introductionmentioning

confidence: 99%

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

“…In mice deficient for the Th17 cell-associated molecules interleukin-17 (IL-17), IL-17 receptor, or IL-23p19, arthritis is markedly suppressed compared with that in their wild-type counterparts (5)(6)(7), and neutralizing antibodies to IL-17 have a therapeutic effect in CIA (8). In humans, some evidence supports the involvement of Th17 cells in the pathogenesis of RA.…”

Section: Conclusion Treatment With Type II Collagenpulsed Tolerogenimentioning

confidence: 99%

Therapeutic effect of tolerogenic dendritic cells in established collagen‐induced arthritis is associated with a reduction in Th17 responses

Stoop¹,

Harry²,

Delwig³

et al. 2010

Arthritis & Rheumatism

124

114

View full text Add to dashboard Cite

Results. Tolerogenic DCs displayed a semimature phenotype, produced low levels of inflammatory cytokines, and exhibited low T cell stimulatory capacity. Upon intravenous injection into arthritic mice, tolerogenic DCs migrated to the spleen, liver, lung, feet, and draining lymph nodes. Treatment of arthritic mice with type II collagen-pulsed tolerogenic DCs, but not unpulsed tolerogenic DCs or mature DCs, significantly inhibited disease severity and progression. This improvement coincided with a significant decrease in the number of Th17 cells and an increase in the number of interleukin-10-producing CD4؉ T cells, whereas tolerogenic DC treatment had no detectable effect on Th1 cells or interleukin-17-producing ␥/␦ T cells.Conclusion. Treatment with type II collagenpulsed tolerogenic DCs decreases the proportion of Th17 cells in arthritic mice and simultaneously reduces the severity and progression of arthritis.

show abstract

Suppression of Immune Induction of Collagen-Induced Arthritis in IL-17-Deficient Mice

Cited by 1,162 publications

References 28 publications

Induction, function and regulation of IL‐17‐producing T cells

Induction, function and regulation of IL‐17‐producing T cells

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

Therapeutic effect of tolerogenic dendritic cells in established collagen‐induced arthritis is associated with a reduction in Th17 responses

Contact Info

Product

Resources

About