Deciphering targets of Th17 cells fate: From metabolism to nuclear receptors

Boldrini, Vinícius O.; Farias, Alessandro S.; Degasperi, Giovanna Rosa

doi:10.1111/sji.12793

Cited by 11 publications

(5 citation statements)

References 108 publications

(214 reference statements)

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“…Taken together, these results suggest that counteracting Th17 development could represent a feasible therapeutic option in PD. The restriction of Th17 development and differentiation can be achieved through different compounds, for example, the peroxisome proliferator-activated receptor-gamma [ 35 ], or through the reduction of transcription factors ROR γ t and STAT3 via cytokines such as IL-4 or IL-32 [ 31 ].…”

Section: Changes Of Peripheral Cd4 + and Cd8 + T Cells In Pd Patientsmentioning

confidence: 99%

T Lymphocytes in Parkinson’s Disease

Contaldi

Magistrelli

Comi

2022

JPD

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T cells are key mediators of both humoral and cellular adaptive immune responses, and their role in Parkinson’s disease (PD) is being increasingly recognized. Several lines of evidence have highlighted how T cells are involved in both the central nervous system and the periphery, leading to a profound imbalance in the immune network in PD patients. This review discusses the involvement of T cells in both preclinical and clinical studies, their importance as feasible biomarkers of motor and non-motor progression of the disease, and recent therapeutic strategies addressing the modulation of T cell response.

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Section: Changes Of Peripheral Cd4 + and Cd8 + T Cells In Pd Patientsmentioning

confidence: 99%

T Lymphocytes in Parkinson’s Disease

Contaldi

Magistrelli

Comi

2022

JPD

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“…Produced by Th-17 cells, it can induce inflammation and attract immune cells [26]. RORγt is a major transcription factor that regulates IL-17A production and Th-17 cell development [27]. IL-23 binds to the receptor IL-23R, which enables the expansion and activation of Th-17 cells [28].…”

Section: Discussionmentioning

confidence: 99%

Umbilical Cord Mesenchymal Stromal/Stem Cells and Their Interplay with Th-17 Cell Response Pathway

Najar,

Rahmani,

Faour

et al. 2024

Cells

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As a form of immunomodulatory therapeutics, mesenchymal stromal/stem cells (MSCs) from umbilical cord (UC) tissue were assessed for their dynamic interplay with the Th-17 immune response pathway. UC-MSCs were able to modulate lymphocyte response by promoting a Th-17-like profile. Such modulation depended on the cell ratio of the cocultures as well as the presence of an inflammatory setting underlying their plasticity. UC-MSCs significantly increased the expression of IL-17A and RORγt but differentially modulated T cell expression of IL-23R. In parallel, the secretion profile of the fifteen factors (IL1β, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-22, IL-21, IL-23, IL-25, IL-31, IL-33, INF-γ, sCD40, and TNF-α) involved in the Th-17 immune response pathway was substantially altered during these cocultures. The modulation of these factors demonstrates the capacity of UC-MSCs to sense and actively respond to tissue challenges. Protein network and functional enrichment analysis indicated that several biological processes, molecular functions, and cellular components linked to distinct Th-17 signaling interactions are involved in several trophic, inflammatory, and immune network responses. These immunological changes and interactions with the Th-17 pathway are likely critical to tissue healing and may help to identify molecular targets that will improve therapeutic strategies involving UC-MSCs.

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“…Th17 cells are known to be regulated by extracellular pH and metabolism. 56 sAC is a sensor of bicarbonate ions and its activity reflects changes in pH and metabolism. 35 sAC may provide a link between these environmental changes and Th17 activity.…”

Section: Inactivation Of Creb Co-activators In T Cells Was Shown To R...mentioning

confidence: 99%

Soluble adenylyl cyclase contributes to imiquimod‐mediated inflammation and is a potential therapeutic target in psoriasis

You

Reilly

Eljalby

et al. 2023

Experimental Dermatology

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Cyclic AMP (cAMP) has a key role in psoriasis pathogenesis, as indicated by the therapeutic efficacy of phosphodiesterase inhibitors that prevent the degradation of cAMP. However, whether soluble adenylate cyclase (sAC) (encoded by the ADCY10 gene), which is an important source for cAMP, is involved in Th17 cell‐mediated inflammation or could be an alternative therapeutic target in psoriasis is unknown. We have utilized the imiquimod model of murine psoriasiform dermatitis to address this question. Adcy10−/− mice had reduced erythema, scaling and swelling in the skin and reduced CD4+ IL17+ cell numbers in the draining lymph nodes, compared with wild‐type mice after induction of psoriasiform dermatitis with imiquimod. Keratinocyte‐specific knock out of Adcy10 had no effect on imiquimod‐induced ear swelling suggesting keratinocyte sAC has no role in imiquimod‐induced inflammation. During Th17 polarization in vitro, naive T cells from Adcy10−/− mice exhibited reduced IL17 secretion and IL‐17+ T‐cell proliferation suggesting that differentiation into Th17 cells is suppressed without sAC activity. Interestingly, loss of sAC did not impact the expression of Th17 lineage‐defining transcription factors (such as Rorc and cMaf) but rather was required for CREB‐dependent gene expression, which is known to support Th17 cell gene expression. Finally, topical application of small molecule sAC inhibitors (sACi) reduced imiquimod‐induced psoriasiform dermatitis and Il17 gene expression in the skin. Collectively, these findings demonstrate that sAC is important for psoriasiform dermatitis in mouse skin. sACi may provide an alternative class of topical therapeutics for Th17‐mediated skin diseases.

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Deciphering targets of Th17 cells fate: From metabolism to nuclear receptors

Cited by 11 publications

References 108 publications

T Lymphocytes in Parkinson’s Disease

T Lymphocytes in Parkinson’s Disease

Umbilical Cord Mesenchymal Stromal/Stem Cells and Their Interplay with Th-17 Cell Response Pathway

Soluble adenylyl cyclase contributes to imiquimod‐mediated inflammation and is a potential therapeutic target in psoriasis

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