Lamtor1 Is Critically Required for CD4⁺ T Cell Proliferation and Regulatory T Cell Suppressive Function

Area of Science:

• Immunology
• Cell Biology
• Molecular Biology

Background:

• Mechanistic target of rapamycin complex 1 (mTORC1) integrates nutrient signals to regulate cellular functions.
• Previous studies on mTORC1 in CD4+ T cells yielded conflicting results.
• Lamtor1's role in T cell amino acid sensing and mTORC1 activation was unexplored.

Purpose of the Study:

• To investigate the function of Lamtor1 in T cells.
• To elucidate the role of Lamtor1 in CD4+ T cell proliferation, cytokine production, and immune cell polarization.
• To determine the in vivo impact of Lamtor1 deficiency on T cell populations and autoimmune disease models.

Main Methods:

• Conditional knockout of Lamtor1 in CD4+ T cells and Foxp3+ T cells using Cre-lox technology in mice.
• Analysis of T cell proliferation, IL-2 production, mTORC1 activity, and gene expression.
• Assessment of Th17, Th1, and Th2 cell polarization.
• Evaluation of T cell numbers, experimental autoimmune encephalomyelitis (EAE) resistance, and regulatory T cell function.

Main Results:

• Lamtor1-deficient CD4+ T cells showed reduced proliferation, IL-2 production, mTORC1 activity, and purine/lipid synthesis gene expression.
• Th17 cell polarization was diminished in Lamtor1-deficient cells.
• Lamtor1-knockout mice were resistant to EAE, with reduced CD4+ and CD8+ T cell numbers.
• Genetic ablation of Lamtor1 in Foxp3+ T cells led to severe autoimmunity and premature death, with impaired regulatory T cell suppressive function and CTLA-4 expression.

Conclusions:

• Lamtor1 is essential for CD4+ T cell function, including proliferation, IL-2 production, and Th17 polarization.
• Lamtor1 plays a critical role in maintaining immune homeostasis and preventing autoimmunity.
• Lamtor1 represents a potential therapeutic target for immune system modulation.