What question did this study set out to answer?

To identify shared molecular mechanisms impairing CD4+ T cell differentiation in patients with STAT3 loss-of-function and STAT1 gain-of-function mutations.

July 14, 2017The Journal of Experimental MedicineOpen Access

PD-L1 up-regulation restrains Th17 cell differentiation in STAT3 loss- and STAT1 gain-of-function patients

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Authors

YZYuan ZhangJilin University CAChi A.National Institutes of Health MLMonica G. LawrenceAsthma Association

Discussion

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Implication

Translational study demonstrates PD-L1 upregulation suppresses Th17 differentiation in STAT3 and STAT1 immunodeficiencies, suggesting PD-L1 inhibition restores immune function.

Key Points

To identify shared molecular mechanisms impairing CD4+ T cell differentiation in patients with STAT3 loss-of-function and STAT1 gain-of-function mutations.
Analyzed cytokine signaling pathways and CD4+ T cell differentiation in patient cohorts with hypomorphic STAT3 or hypermorphic STAT1 mutations.
Evaluated STAT1 phosphorylation and PD-L1 upregulation in vitro, testing the regulatory impact of SOCS3 overexpression.
Assessed Th17 rescue using in vitro PD-L1 blockade and an in vivo STAT3 loss-of-function mouse model crossed with PD-1 knockout mice.
Cytokine stimulation induced STAT1 hyperphosphorylation and marked STAT1-dependent PD-L1 upregulation in both patient cohorts, impairing Th17 cell differentiation.
Overexpression of SOCS3 strongly inhibited both STAT1 phosphorylation and PD-L1 upregulation, implicating reduced SOCS3 activity in the defect.
Inhibiting PD-L1 in vitro or genetically knocking out PD-1 in STAT3-deficient mice partially rescued Th17 cell differentiation.

Cite This Study

Zhang et al. (2017) studied this question.

synapsesocial.com/papers/6a1a047e443d3ecd7cdf43c4 https://doi.org/10.1084/jem.20161427

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Implication

Translational study demonstrates PD-L1 upregulation suppresses Th17 differentiation in STAT3 and STAT1 immunodeficiencies, suggesting PD-L1 inhibition restores immune function.

PD-L1 up-regulation restrains Th17 cell differentiation in STAT3 loss- and STAT1 gain-of-function patients

Discussion

Member takes

Implication

Key Points

Cite This Study

PD-L1 up-regulation restrains Th17 cell differentiation in STAT3 loss- and STAT1 gain-of-function patients

Discussion

Member takes

Implication

Key Points

Cite This Study

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