What question did this study set out to answer?

To delineate the distinct roles of mTORC1 and mTORC2 signaling pathways in governing T cell lineage differentiation and regulatory T cell populations in systemic lupus erythematosus.

March 29, 2014The Journal of ImmunologyOpen Access

Mechanistic Target of Rapamycin Complex 1 Expands Th17 and IL-4+ CD4−CD8− Double-Negative T Cells and Contracts Regulatory T Cells in Systemic Lupus Erythematosus

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Authors

HKHiroshi KatoSUNY Upstate Medical University APAndrás PerlSUNY Upstate Medical University

Discussion

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Implication

Controlled laboratory study demonstrates that mTORC1 activation skews T cell lineage balance in systemic lupus erythematosus, highlighting therapeutic targets for immune regulation.

Key Points

To delineate the distinct roles of mTORC1 and mTORC2 signaling pathways in governing T cell lineage differentiation and regulatory T cell populations in systemic lupus erythematosus.
Analyzed mTORC1 and mTORC2 activity in T cell subsets from systemic lupus erythematosus (SLE) patients and matched healthy controls (HC) by quantifying substrate phosphorylation.
Cultured T cells for 3 days in vitro with or without rapamycin or cytokine-neutralizing antibodies to evaluate GATA-3, IFN-γ, IL-4, IL-17, and regulatory T cell (Treg) frequencies.
mTORC1 activity was increased and mTORC2 decreased in SLE; rapamycin suppressed elevated IL-4 in stimulated double-negative T cells (control: 9.26 ± 1.48% vs rapamycin: 5.03 ± 0.66%, p < 0.001) and CD4+ IL-17 expression (control: 3.91 ± 0.79% vs rapamycin: 2.22 ± 0.60%, p < 0.001).
Lupus patients had lower Treg frequencies than healthy controls (1.83 ± 0.25% vs 2.97 ± 0.27%, p = 0.0012), but inhibiting mTORC1 with rapamycin or neutralizing IL-17 successfully restored Treg expansion.

Cite This Study

Kato et al. (2014) studied this question.

synapsesocial.com/papers/69fd0526ea4a61241c5d074a https://doi.org/10.4049/jimmunol.1301859

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Implication

Controlled laboratory study demonstrates that mTORC1 activation skews T cell lineage balance in systemic lupus erythematosus, highlighting therapeutic targets for immune regulation.

Mechanistic Target of Rapamycin Complex 1 Expands Th17 and IL-4+ CD4−CD8− Double-Negative T Cells and Contracts Regulatory T Cells in Systemic Lupus Erythematosus

Discussion

Member takes

Implication

Key Points

Cite This Study

Mechanistic Target of Rapamycin Complex 1 Expands Th17 and IL-4+ CD4−CD8− Double-Negative T Cells and Contracts Regulatory T Cells in Systemic Lupus Erythematosus

Discussion

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Implication

Key Points

Cite This Study

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