Balance of Th1 and Th17 effector and peripheral regulatory T cells

Lohr, Jens G.; Knoechel, Birgit; Caretto, David; Abbas, Abul K.

doi:10.1016/j.micinf.2009.04.012

Cited by 36 publications

(26 citation statements)

References 33 publications

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“…In untreated sOVA-Tg mice, DO11.10 cells failed to produce high levels of cytokines, as previously reported (7,8,24) (Fig. 2A, 2B).…”

Section: Cd40 Activation Specifically Induces An Il-17 Responsesupporting

confidence: 87%

“…Additionally, the generation of Th1 and Th17 effector cells has been shown to be dependent on various other parameters including transcription factors, epigenetic modifications, and CD28 costimulation (2)(3)(4)(5). There is also evidence for temporal differences in the appearance of Th1 and Th17 cells, with most studies showing that the Th17 response peaks early, followed by the appearance of Th1 cells (6)(7)(8)(9). Finally, the development of these subsets is reciprocally regulated, due mainly to the fact that IFN-g is a powerful inhibitor of Th17 differentiation (3,10).…”

Section: Ifferent Subsets Of Effector Cd4mentioning

confidence: 99%

“…Interaction of these Ag-specific T cells with their cognate Ag in a lymphopenic host (sOVA-Tg/Rag 2/2 ) leads to a failure of tolerance, T cell activation, and a systemic inflammatory disease. During the propagation of this inflammatory disease there is uncontrolled activation of self-reactive DO11.10 cells, resulting in massive proliferation and the production of IFN-g and IL-17 (7)(8)(9). In the absence of B7 expression in the host, there is a failure to initiate an effector response from Ag-specific T cells, implying an essential contribution of B7 + APCs, presumably DCs, in the generation of cytokine-producing cells (15).…”

Section: Ifferent Subsets Of Effector Cd4mentioning

confidence: 99%

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Differential Requirements for Th1 and Th17 Responses to a Systemic Self-Antigen

Katzman

Gallo

Hoyer

et al. 2011

The Journal of Immunology

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T cell–APC interactions are essential for the initiation of effector responses against foreign and self-antigens, but the role of these interactions in generating different populations of effector T cells in vivo remains unclear. Using a model of CD4+ T cell responses to a systemic self-antigen without adjuvants or infection, we demonstrate that activation of APCs augments Th17 responses much more than Th1 responses. Recognition of systemic Ag induces tolerance in self-reactive CD4+ T cells, but induction of CD40 signaling, even under tolerogenic conditions, results in a strong, Ag-specific IL-17 response without large numbers of IFN-γ–producing cells. Transfer of the same CD4+ T cells into lymphopenic recipients expressing the self-antigen results in uncontrolled production of IL-17, IFN-γ, and systemic inflammation. If the Ag-specific T cells lack CD40L, production of IL-17 but not IFN-γ is decreased, and the survival time of recipient mice is significantly increased. In addition, transient blockade of the initial MHC class II-dependent T cell–APC interaction results in a greater reduction of IL-17 than of IFN-γ production. These data suggest that Th17 differentiation is more sensitive to T cell interactions with APCs than is the Th1 response, and interrupting this interaction, specifically the CD40 pathway, may be key to controlling Th17-mediated autoimmunity.

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“…In untreated sOVA-Tg mice, DO11.10 cells failed to produce high levels of cytokines, as previously reported (7,8,24) (Fig. 2A, 2B).…”

Section: Cd40 Activation Specifically Induces An Il-17 Responsesupporting

confidence: 87%

Section: Ifferent Subsets Of Effector Cd4mentioning

confidence: 99%

Section: Ifferent Subsets Of Effector Cd4mentioning

confidence: 99%

See 1 more Smart Citation

Differential Requirements for Th1 and Th17 Responses to a Systemic Self-Antigen

Katzman

Gallo

Hoyer

et al. 2011

The Journal of Immunology

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“…Although Th1 cytokines were unaltered, the observation of mild enhancement of the Th2 cytokines IL-4 and IL-5 in cultures of T cells from CD69 KO mice, together with the effect of CD69-mediated suppression of IL-17, could be linked by the expression of transcription factor c-Maf, which has been involved in both Th2 and Th17 differentiation (2). In this regard, it has been recently proposed that Th17 polarization would result from a default response in CD4 T-cell differentiation, actively modified to give Th1 and Treg (19). Our data suggest that early induction of CD69 in T cells would facilitate the inhibition of the "natural tendency" to generate Th17, allowing other outcomes in the differentiation process.…”

Section: Discussionmentioning

confidence: 99%

CD69 Association with Jak3/Stat5 Proteins Regulates Th17 Cell Differentiation

Martı́n

Gómez

Lamana

et al. 2010

Molecular and Cellular Biology

111

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Differentiation of T helper lymphocyte subsets is crucial for immune and inflammatory responses. In addition to the two classical T helper cell subsets (Th1 and Th2), a third T-lymphocyte subpopulation, designated Th17, characterized by the synthesis of interleukin 17A (IL-17A), IL-17F, and IL-22, has emerged as an independent differentiation pathway (9). Differentiation toward each Th subset is regulated by a variety of molecules, including cytokines and transcription factors. The key transcription factors that drive the differentiation of the Th1 and Th2 lineages are, respectively, T-bet and GATA-3, while the differentiation of Th17 cells is directed by retinoic acid-related orphan receptor ␥t (ROR␥t) (12). Th17 differentiation, moreover, is regulated by the balance of Stat3/Stat5 activation; Stat3 is necessary for Th17 differentiation, whereas the transcription factor Stat5 negatively regulates the development of these cells (1). The key cytokines involved in Th17 cell differentiation are transforming growth factor ␤ (TGF-␤) and IL-6 (3, 33). Another important cytokine for Th17 biology is IL-23. Although Th17 cells can arise in the absence of IL-23, the cytokine is required for their maintenance and survival (29, 33) and for their pathogenicity (20).Dysregulated activation of T helper subpopulations is associated with immune pathogenesis (21). Th1 cells are clearly involved in autoimmune and inflammatory disorders mediated by the cellular immune response, and Th2 cells are involved in antibody-mediated allergic and inflammatory conditions (24).Recent evidence indicates that Th17 cells also exert a pathogenic effect in several autoimmune and hypersensitivity reactions. Indeed, a number of immune pathologies previously thought to be related to uncontrolled activation of Th1 or Th2 populations now appear to be related, at least in part, to Th17 cell differentiation. For example, involvement of Th17 lymphocytes has been reported in collagen-induced arthritis (CIA), experimental autoimmune encephalomyelitis (EAE), experimental autoimmune myocarditis (EAM), contact hypersensitivity (CHS), and airway hyperresponsiveness (AHR) (11,13,18,22,23,30).We previously found that CD69 ϩ T cells are localized at sites of chronic inflammation and that these lymphocytes seem to be able to downregulate the inflammatory process. Although antigen-dependent T-cell activation and proliferation do not appear to be altered in CD69-deficient lymphocytes (16), CD69 knockout (CD69 KO) mice develop an exacerbated form of CIA characterized by diminished local synthesis of TGF-␤ (26). These and other studies (5) suggest that CD69 is a negative regulator of the immune response, in part through modulation of local levels of TGF-␤. Here, we explore the role of CD69 in the differentiation of T helper lineages. Our results show that, while Th1 and Th2 differentiation remain unchanged in CD69-deficient mice, lymphocytes from these animals show an enhanced potential to differentiate toward Th17 cells both in vitro and in vivo. Biochemical and funct...

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“…(7) obesity was associated with higher blood concentrations of IL-17/ IL-23 axis. IL-17 is a potent pleiotropic pro-inflammatory cytokine that participates in tissue inflammation by activating several cytokines, matrix metalloproteases and stimulating neutrophils proliferation and migration and its concentrations is increased in sera and tissue of several autoimmune disease such as rheumatoid arthritis, multiple sclerosis and inflammatory bowel disease (8,9). On the other hand, regulatory T-cells (Treg) have antiinflammatory effect and can suppress autoimmunity by releasing anti-inflammatory cytokines (TGF-β and IL-10) (10).…”

Section: Introductionmentioning

confidence: 99%

Vitamin A supplementation reduces the Th17-Treg – Related cytokines in obese and non-obese women

Farhangi

Saboor-Yaraghi

Keshavarz

2016

Arch. Endocrinol. Metab.

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Objective: The objective of the present study was to investigate the effect of vitamin A supplementation on serum Th17 (IL-6, IL-17, IFNγ) and Treg (TGF-β, IL-10) related cytokines in obese and non-obese women. Subjects and methods: In a randomized double blind placebo controlled design, 56 obese women were randomly assigned to receive either an oral dose of 25,000 IU retinyl palmitate or placebo per day for 4 months. Twenty eight ages matched non-obese women were also received vitamin A. At the study entry, anthropometric variables were measured and serum Th17 and Treg related cytokine profile were determined at baseline and 4 months after intervention. Results: Significantly higher baseline concentrations of IL-6 were observed in obese compared with non-obese women (P < 0.05). However, the initial concentrations of other cytokines were not significantly different between groups. The mean concentrations of IL-17 and TGF-β were significantly decreased after vitamin A supplementation in non-obese and obese women respectively. Positive relationships between IL-17 and IL-10 (r = 0.42, P < 0.001), TGF-β and IL-17 (r = 0.35, P < 0.001) and between IL-10 and IFN-γ (r = 0.41, P = 0.002) in total participants were also observed. Conclusions: The results of the present study showed for the first time that vitamin A supplementation reduces serum concentrations of IL-17 and TGF-β in reproductive age women. Further studies are needed to explore the possible underlying mechanisms. Arch Endocrinol Metab. 2016;60(1): [29][30][31][32][33][34][35]

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Balance of Th1 and Th17 effector and peripheral regulatory T cells

Cited by 36 publications

References 33 publications

Differential Requirements for Th1 and Th17 Responses to a Systemic Self-Antigen

Differential Requirements for Th1 and Th17 Responses to a Systemic Self-Antigen

CD69 Association with Jak3/Stat5 Proteins Regulates Th17 Cell Differentiation

Vitamin A supplementation reduces the Th17-Treg – Related cytokines in obese and non-obese women

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