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

Abstract

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]....

Interleukin‐10 plays a key role in the modulation of neutrophils recruitment and lung inflammation during infection by Streptococcus pneumoniae

“…1,11,12 In contrast, IFN-c is thought to inhibit Th17 immune responses. 30 As the effect of the presence or absence of IL-10 in the proinflammatory pattern was observed at 48 hpi, without significant changes in the frequency of T cells, it is likely that IL-10 is required for the proper secretion of cytokines by innate and epithelial cells, which will in turn promote a Th17 response profile. 30 Our data show that the lack of IL-10 during S. pneumoniae infection, leads to higher levels of IFN-c and TNF-a, which might inhibit the development of Th17 immune responses and lead to an exacerbated innate inflammation.…”

Relationship between vitamin D and IL-23, IL-17 and macrophage chemoattractant protein-1 as markers of fibrosis in hepatitis C virus Egyptians

“…Regulation of Th1 and Th17 responses in HCVinfected individuals was studied, and it was reported that TGF-β and IL-6 promote differentiation of naive murine CD4 + T cells into IL-17-secreting Th17 cells. In addition, it has been reported that other innate cytokines, including IL-1, IL-23, TNF-α, and IL-21, in different combinations or with TGF-β, are also involved in differentiation, amplification, or stabilization of the Th17 phenotype [17,18] .…”

Measurement of Serum Levels of Interleukin 17 and 23 in the Immune System with Different Amounts of Spleens White Pulp Size after Inoculation of New Leishmania Vaccine in Susceptible Mice

“…In the presence of interleukin 17 nitrite oxide synthase (iNOS) can produce nitrite oxide [11]. It also stimulates production of pro inflammatory cytokines (TNF-alpha, IL-1-beta), inflammatory chemokines to elevation of phagocytosis and effect on neutrophils and macrophages [12,13]. Neutrophils in leishmaniasis are very important in remove of parasites [13], but its short life cause serve only as "Trojan Horse" to avoid destruction by immune system [14].…”