Th17: An effector CD4 T cell lineage with regulatory T cell ties

Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Immunity (Impact Factor: 21.56). 07/2006; 24(6):677-88. DOI: 10.1016/j.immuni.2006.06.002
Source: PubMed


The naive CD4 T cell is a multipotential precursor with defined antigen recognition specificity but substantial plasticity for development down distinct effector or regulatory lineages, contingent upon signals from cells of the innate immune system. The range of identified effector CD4 T cell lineages has recently expanded with description of an IL-17-producing subset, called Th17, which develops via cytokine signals distinct from, and antagonized by, products of the Th1 and Th2 lineages. Remarkably, Th17 development depends on the pleiotropic cytokine TGF-beta, which is also linked to regulatory T cell development and function, providing a unique mechanism for matching CD4 T cell effector and regulatory lineage specification. Here, we review Th17 lineage development, emphasizing similarities and differences with established effector and regulatory T cell developmental programs that have important implications for immune regulation, immune pathogenesis, and host defense.

1 Follower
22 Reads
  • Source
    • "The IL-17 family contains six members, IL-17A, IL-17B, IL- 17C, IL-17D, IL-17E (or IL-25), and IL-17F, and five receptors, IL-17RA–RD and SEF. Interleukin-17A is most homologous to IL-17F and the genes encoding them are proximally located on chromosome 6p12 [15]. The IL-17F activity is similar to IL- 17A but significantly weaker and is related to inducing the expression of various cytokines, chemokines, matrix metalloproteinases , antimicrobial peptides, and adhesion molecules by human fibroblasts, airway epithelial cells, and vein endothelial cells [16]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: A case-control study was conducted on patients with chronic periodontitis (CP) and healthy controls with the aim of evaluating possible association between interleukin 17A (IL17A) G197A (rs2275913) and IL17F T7488C (rs763780) polymorphisms and periodontitis. Genotypes were determined by PCR-RFLP method. Statistical analyses were conducted using the OpenEpi and SNPStas software to calculate Chi-square with Yates correction or Fisher's exact tests, odds ratios (OR), and 95% confidence intervals (CIs). SNPStas software was used to calculate Hardy-Weinberg equilibrium. IL17A AA genotype was more frequent in patients with chronic periodontitis (CP) in the codominant and recessive models (= 0.09; OR = 2.53 and = 0.03; OR = 2.46, resp.), the females with CP (= 0.01, OR = 4.34), Caucasoid patients with CP (= 0.01, OR = 3.45), and nonsmoking Caucasian patients with CP (= 0.04, OR = 3.51). The IL17A A allele was also more frequent in Caucasians with CP (= 0.04, OR = 1.59). IL17F T7488C polymorphism was not associated with chronic periodontitis. In these patients from Southern Brazil, the IL17A rs2275913 polymorphisms, IL17A AA genotype, and the A allele were associated with a susceptibility to chronic periodontitis.
    Mediators of Inflammation 09/2015; 2015:1-8. DOI:10.1155/2015/147056 · 3.24 Impact Factor
  • Source
    • "We used to think that the responding T cells exhibit a T-helper (Th) cell type 1 phenotype capable of producing IFN-í µí»¾ in CD [3], whereas Th2 cytokine, such as IL-4, IL-5, or IL-13, is closely associated with UC [4]. In addition to these major immune responses associated with CD and UC, Th17, which mainly produces IL-17A, has also been linked to pathogenesis of IBD recently [5] [6]. Among various experimentally induced colitis models in mice, dextran sulphate sodium-(DSS-) induced acute or chronic colitis is the most commonly used as IBD animal models [7] [8]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Interleukin- (IL-) 33, a member of the IL-1 cytokine family, is an important modulator of the immune system associated with several immune-mediated diseases. IL-33 was expressed in high level on epithelial cells of intestinal tract. It suggested that IL-33 plays a potential role in inflammatory bowel diseases (IBD). We investigated the role of interleukin- (IL-) 33 in dextran sulphate sodium- (DSS-) induced acute colitis in mice using recombinant mouse IL-33 protein (rIL-33). We found that DSS-induced acute colitis was aggravated by rIL-33 treatment. rIL-33-treated DSS mice showed markedly reduced levels of interferon- (IFN-)γ and IL-17A in their colon lamina propria lymphocytes (LPL), but the levels of Th2 cytokines, such as IL-5 and IL-13, in these cells were significantly increased, compared to DSS mice treated with PBS. Our results suggested that IL-33 stimulated CD4+T cells and caused the cell to adopt a Th2-type response but at the same time suppressed Th17 and Th1 cell responses. Therefore, IL-33 may be involved in pathogenesis of DSS-induced acute colitis by promoting Th2 cell response in intestinal mucosa of mice. Modulation of IL-33/ST2 signaling by monoclonal antibody (mAb) could be a novel biological therapy in DSS-induced acute colitis.
    Mediators of Inflammation 07/2015; 2015:1-12. DOI:10.1155/2015/913041 · 3.24 Impact Factor
  • Source
    • "A major role in vitiligo cellular immunity is displayed by Th1 and Th17 populations of lymphocytes in combination with the suppression of TREGs and Th2 populations [4] [5]. This agrees with a new hypothesis that suggests the skewing of responses toward Th17 or Th1 with respect to TREGs and Th2 cells as a trigger event for the development and progression of autoimmune diseases [6] [7]. Skin lesional (depigmented) areas in vitiligo patients are characterized by a massive infiltration of inflammatory cells (particularly cytotoxic), T-helper cells and macrophages. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Vitiligo is a systemic dermatological disorder characterized by the loss of skin pigmentation due to melanocyte injury or aberrant functioning. Recent data underline its multifactorial etiology with significant involvement of autoimmune and redox alterations. The major role in vitiligo cellular immunity is displayed by augmented Th1 and Th17 and suppressed TREGs and Th2 lymphocyte populations. Our previous studies indicate a marked redox imbalance in perilesional (“PL”, i.e. obtained from visibly unaffected skin surrounding the depigmented area in vitiligo patients) keratinocytes where the massive infiltration of inflammatory cells takes place. No defined therapy exists for vitiligo. Although a number of approaches have been used for the induction of TREGs and Th2 cells, they may be associated with significant off-target effects.
    Journal of dermatological science 05/2015; 79(2). DOI:10.1016/j.jdermsci.2015.05.003 · 3.42 Impact Factor
Show more

Preview (2 Sources)

22 Reads
Available from