What question did this study set out to answer?

Investigate how T cell receptor (TCR) signaling coordinates with cytokine signals to promote STAT3 phosphorylation and determine TH17 versus Treg cell differentiation.

January 19, 2024The Journal of Experimental MedicineOpen Access

TCR signaling induces STAT3 phosphorylation to promote TH17 cell differentiation

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Authors

ZQZhen QinAnhui Normal University RWRuining WangHenan University PHPing HouGuangxi Normal University

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Implication

Experimental study reveals that TCR signaling mediates STAT3 phosphorylation through Lck/Fyn in T cells, indicating a targeted therapeutic strategy for TH17-driven autoimmune diseases.

Key Points

Investigate how T cell receptor (TCR) signaling coordinates with cytokine signals to promote STAT3 phosphorylation and determine TH17 versus Treg cell differentiation.
Measured STAT3 phosphorylation at tyrosine 705 in T cells activated via TCR stimulation, cytokine exposure (IL-6/IL-23), or both.
Inhibited Lck/Fyn kinase activity using the small molecule Srci1 and evaluated disease-associated STAT3 mutations that disrupt Lck/Fyn binding.
Assessed T cell fate specification into TH17 or FOXP3+ Treg cells in vitro and monitored disease severity in an experimental autoimmune encephalomyelitis (EAE) mouse model.
TCR stimulation alone initiated STAT3 phosphorylation via Lck/Fyn kinases and acted synergistically with IL-6 and IL-23 to induce robust STAT3 Y705 phosphorylation.
Inhibition of Lck/Fyn with Srci1 or disruption of the Lck/Fyn-STAT3 interaction selectively abrogated TCR-dependent STAT3 phosphorylation, preventing TH17 cell differentiation and promoting conversion to FOXP3+ Treg cells.
Pharmacological inhibition via Srci1 or genetic disruption of Lck/Fyn-STAT3 binding significantly attenuated clinical disease in TH17-mediated experimental autoimmune encephalomyelitis.

Cite This Study

Qin et al. (2024) studied this question.

synapsesocial.com/papers/6a74c98d0081fe7b05dbea6c https://doi.org/10.1084/jem.20230683

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Implication

Experimental study reveals that TCR signaling mediates STAT3 phosphorylation through Lck/Fyn in T cells, indicating a targeted therapeutic strategy for TH17-driven autoimmune diseases.

TCR signaling induces STAT3 phosphorylation to promote TH17 cell differentiation

Discussion

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Implication

Key Points

Cite This Study

TCR signaling induces STAT3 phosphorylation to promote TH17 cell differentiation

Discussion

Member takes

Implication

Key Points

Cite This Study

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