Biological and clinical significance of T helper 17 cell plasticity

Mazzoni, Alessio; Maggi, Laura; Liotta, Francesco; Cosmi, Lorenzo; Annunziato, Francesco

doi:10.1111/imm.13124

Cited by 42 publications

(69 citation statements)

References 99 publications

(208 reference statements)

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“…Inflammatory cytokines are important factors in deciding the fate of activated naive cells. In particular, cytokines such as IL-6 and IL-1b, in combination with TGF-b, may lead to enhanced differentiation toward the pathogenic T H 17 subset (53). In this regard, the increased IL-6 production observed with vitamin D treatment may also influence T cell differentiation to a phenotype that would be undesired in the context of autoimmunity.…”

Section: Discussionmentioning

confidence: 99%

Vitamin D and IFN-β Modulate the Inflammatory Gene Expression Program of Primary Human T Lymphocytes

et al. 2020

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IFN-β treatment is a commonly used therapy for relapsing-remitting multiple sclerosis (MS), while vitamin D deficiency correlates with an increased risk of MS and/or its activity. MS is a demyelinating chronic inflammatory disease of the central nervous system, in which activated T lymphocytes play a major role, and may represent direct targets of IFN-β and vitamin D activities. However, the underlying mechanism of action of vitamin D and IFN-β, alone or in combination, remains incompletely understood, especially when considering their direct effects on the ability of T lymphocytes to produce inflammatory cytokines. We profiled the expression of immune-related genes and microRNAs in primary human T lymphocytes in response to vitamin D and IFN-β, and we dissected the impact of these treatments on cytokine production and T cell proliferation. We found that the treatments influenced primarily memory T cell plasticity, rather than polarization toward a stable phenotype. Moreover, our data revealed extensive reprogramming of the transcriptional output of primary T cells in response to vitamin D and IFN-β and provide the bases for further mechanistic insights into these commonly used treatments.

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Section: Discussionmentioning

confidence: 99%

Vitamin D and IFN-β Modulate the Inflammatory Gene Expression Program of Primary Human T Lymphocytes

et al. 2020

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“…These results indicate PDT‐mediated activation of a type 3 immunity that leads to type 1 immunity via inflammation characterized by neutrophilia. The mechanism of this switch is unclear but may be related to the inherent plasticity of Th17 cells (87).…”

Section: Components Of Pdt: Photosensitizer Light and Molecular Oxygenmentioning

confidence: 99%

Photodynamic Therapy and Immunity: An Update

Falk-Mahapatra

Gollnick

2020

Photochem & Photobiology

129

110

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Dr. Thomas Dougherty and his Oncology Foundation of Buffalo were the first to support my (S.O.G.) research into the effects of photodynamic therapy (PDT) on the host immune system. The small grant I was awarded in 2002 launched my career as an independent researcher; at the time, there were few studies on the importance of the immune response on the efficacy of PDT and no studies demonstrating the ability of PDT to enhance antitumor immunity. Over the last decades, the interest in PDT as an enhancer of antitumor immunity and our understanding of the mechanisms by which PDT enhances antitumor immunity have dramatically increased. In this review article, we look back on the studies that laid the foundation for our understanding and provide an update on current advances and therapies that take advantage of PDT enhancement of immunity.

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“…Moreover, fate-mapping experiments demonstrated that Th17 cells in the CNS co-express or exclusively express interferon (IFN)γ [23,24]. This led to the conclusion that Th17 cells can switch to an IFNγ-producing, ex-Th17 phenotype [25][26][27]. The molecular mechanisms of Th17 cell plasticity have been shown to be highly dependent on the tissue environment of the cells [26,[28][29][30][31][32][33], while the prerequisites shaping T cell phenotypes within the CNS tissue remain poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Functional characteristics of Th1, Th17, and ex-Th17 cells in EAE revealed by intravital two-photon microscopy

Loos

Schmaul

Noll

et al. 2020

J Neuroinflammation

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Background T helper (Th) 17 cells are a highly plastic subset of T cells, which in the context of neuroinflammation, are able to acquire pathogenic features originally attributed to Th1 cells (resulting in so called ex-Th17 cells). Thus, a strict separation between the two T cell subsets in the context of experimental autoimmune encephalomyelitis (EAE) is difficult. High variability in culture and EAE induction protocols contributed to previous conflicting results concerning the differential contribution of Th1 and Th17 cells in EAE. Here, we systematically evaluate the role of different T cell differentiation and transfer protocols for EAE disease development and investigate the functional dynamics of encephalitogenic T cells directly within the inflamed central nervous system (CNS) tissue. Methods We compiled the currently used EAE induction protocols reported in literature and investigated the influence of the different Th1 and Th17 differentiation protocols as well as EAE induction protocols on the EAE disease course. Moreover, we assessed the cytokine profile and functional dynamics of both encephalitogenic Th1 and Th17 cells in the inflamed CNS using flow cytometry and intravital two-photon laser scanning microscopy. Lastly, we used astrocyte culture and adoptive transfer EAE to evaluate the impact of Th1 and Th17 cells on astrocyte adhesion molecule expression in vitro and in vivo. Results We show that EAE courses are highly dependent on in vitro differentiation and transfer protocols. Moreover, using genetically encoded reporter mice (B6.IL17A-EGFP.acRFP x 2d2/2d2.RFP), we show that the motility of interferon (IFN)γ-producing ex-Th17 cells more closely resembles Th1 cells than Th17 cells in transfer EAE. Mechanistically, IFNγ-producing Th1 cells selectively induce the expression of cellular adhesion molecules I-CAM1 while Th1 as well as ex-Th17 induce V-CAM1 on astrocytes. Conclusions The behavior of ex-Th17 cells in EAE lesions in vivo resembles Th1 rather than Th17 cells, underlining that their change in cytokine production is associated with functional phenotype alterations of these cells.

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Biological and clinical significance of T helper 17 cell plasticity

Cited by 42 publications

References 99 publications

Vitamin D and IFN-β Modulate the Inflammatory Gene Expression Program of Primary Human T Lymphocytes

Vitamin D and IFN-β Modulate the Inflammatory Gene Expression Program of Primary Human T Lymphocytes

Photodynamic Therapy and Immunity: An Update

Functional characteristics of Th1, Th17, and ex-Th17 cells in EAE revealed by intravital two-photon microscopy

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