IL-17 Production Is Dominated by γδ T Cells rather than CD4 T Cells during <i>Mycobacterium tuberculosis</i> Infection

Lockhart, Euan; Green, Angela M.; Flynn, JoAnne L.

doi:10.4049/jimmunol.177.7.4662

Cited by 690 publications

(609 citation statements)

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“…Th cells producing IL-17 (Th17 cells) are a distinct subset of effector cells that differentiate from naive T cells in response to IL-6 and TGF-b [25,26], whereas IL-23 serves as an important factor to expand previously differentiated Th17 cell populations and gd T cells [27,28]. Our data showed that C5a significantly increased IL-17 production by T lymphocytes in the presence of DC, while it had no influence on IL-17 production from T lymphocyte when DC were absent.…”

Section: Discussionmentioning

confidence: 99%

Complement C5a regulates IL‐17 by affecting the crosstalk between DC and γδ T cells in CLP‐induced sepsis

Xu¹,

Wang²,

Han³

et al. 2010

Eur J Immunol

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Complement 5a (C5a) and are two important inflammatory mediators in sepsis. Here we studied the mechanisms underlying regulation of IL-17 by anaphylatoxin C5a. We found that C5a blockade increased the survival rate of mice following cecal ligation and puncture (CLP)-induced sepsis and decreased IL-17 expression in vivo. IL-17 was secreted mainly by cd T cells in this model. Importantly, our data suggest that C5a participates in the regulation of IL-17 secretion by cd T cells. Dendritic cells (DC) were found to act as a ''bridge'' between C5a and cd T cells in a mechanism involving IL-6 and transforming growth factor b (TGF-b). These results imply that C5a affects the crosstalk between DC and cd T cells during sepsis development, and this may result in a large production of inflammatory mediators such as IL-17.Key words: Complement system . gd T cells . Immunopathology IntroductionSepsis is a life-threatening medical condition caused by various microorganisms entering the human bloodstream and triggering an uncontrolled inflammatory reaction. In light of the multifactorial pathogenesis of sepsis, extensive work has been done to characterize the numerous agents and mediators that are involved in sepsis. In spite of extensive research efforts over the last 20 years, sepsis remains the leading cause of death in intensive care units [1,2]. Specific therapies are generally unavailable because pathogenic mechanisms are still unclear.There is abundant evidence that complement activation, production of cytokines and other inflammatory responses occur in sepsis [3]. It is generally accepted that the complement activation product complement 5a (C5a) plays an important inflammatory role in rodents following cecal ligation and puncture (CLP) [4]. C5a exerts its effects through the high-affinity C5a receptor (C5aR) and C5L2. C5L2, a putative ''default'' receptor, has been suggested to play important role in balancing the biological effect of C5a. For example, recent data showed that both C5aR and C5l2 cooperatively play functional parts in the setting of sepsis [5]. It has been shown that blockade of C5a or its receptor (C5aR) can inhibit the development of CLP and is associated with decreased levels of bacteria, preservation of innate immune functions of blood neutrophils, reduced thymocyte apoptosis and greatly improved survival rates [6,7].IL-17 (also known as IL-17A) is a proinflammatory cytokine produced by a variety of cells including CD4 1 Th17 cells, CD8 1 T cells, neutrophils and NK cells [8]. Recent reports also suggested that gd T cells are a major source of . Although it has been demonstrated that IL-17 plays an important role in Ã These authors contributed equally to this paper. Understanding crosstalk between critical pathogenic factors may be very important for designing treatments for sepsis. Here, we studied the crosstalk between two critical pathogenic factors, C5a and IL-17. Our results show that C5a acted on DC, which subsequently induced gd T cells to secrete IL-17. ResultsC5a induced IL-17 in CLP-induce...

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Section: Discussionmentioning

confidence: 99%

Complement C5a regulates IL‐17 by affecting the crosstalk between DC and γδ T cells in CLP‐induced sepsis

Xu¹,

Wang²,

Han³

et al. 2010

Eur J Immunol

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“…γδ 17 cells produce much more IL‐17 than Th17 cells after Mycobacterium tuberculosis 78 or Mycobacterium bovis BCG infection 79. Expression of IL‐17 is detected in lungs from the first day after infection with BCG and induces not only neutrophil‐mediated inflammation but also granuloma formation 79.…”

Section: γδ17 Cells In Pathogen Clearancementioning

confidence: 99%

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

Akitsu

Iwakura

2018

Immunology

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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.

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“…gd T cells and other non-CD4 1 CD8 1 T cells are the primary source of IL-17 during Mycobacterium tuberculosis infection [28]. Vd1 1 gd T cells are also a major source of IL-17 in Escherichia coli infection, where they promote neutrophil recruitment [29].…”

Section: T-cell Subtypes That Secrete Il-17mentioning

confidence: 99%

“…Unconventional T cells can also secrete IL-17 when activated with appropriate stimuli in vitro or in vivo during infection or inflammation [27][28][29][30]. Invariant NKT cells that lack the NK1.1 marker have been found to secrete high concentrations of IL-17, but not IFN-g, and to mediate neutrophil influx into the lungs during airway inflammation [27].…”

Section: T-cell Subtypes That Secrete Il-17mentioning

confidence: 99%

“…It has recently been demonstrated that NKT cells, which express IL-23R, secrete IL-17 following stimulation with anti-CD3 and IL-23, independently of . Furthermore, NKT cells can secrete IL-17 in response to the synthetic ligand a-galactosylceramide [27,30].gd T cells and other non-CD4 1 CD8 1 T cells are the primary source of IL-17 during Mycobacterium tuberculosis infection [28]. Vd1 1 gd T cells are also a major source of IL-17 in Escherichia coli infection, where they promote neutrophil recruitment [29].…”

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

2008

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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]....

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IL-17 Production Is Dominated by γδ T Cells rather than CD4 T Cells during Mycobacterium tuberculosis Infection

Cited by 690 publications

References 28 publications

Complement C5a regulates IL‐17 by affecting the crosstalk between DC and γδ T cells in CLP‐induced sepsis

Complement C5a regulates IL‐17 by affecting the crosstalk between DC and γδ T cells in CLP‐induced sepsis

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

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

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