Macropinocytosis drives T cell growth by sustaining the activation of mTORC1

Area of Science:

• Cell Biology
• Immunology
• Molecular Biology

Background:

• Macropinocytosis is a conserved endocytic process with known roles in antigen presentation and tumor growth.
• Its role in the expansion of non-transformed mammalian cells, particularly T cells, remains largely unexplored.

Purpose of the Study:

• To investigate the role of macropinocytosis in the growth and expansion of primary mouse and human T cells.
• To elucidate the underlying molecular mechanisms, including the involvement of mTORC1 signaling.

Main Methods:

• Primary mouse and human T cells were utilized.
• Macropinocytosis levels were assessed upon T cell activation.
• The impact of macropinocytosis on T cell growth and mTORC1 activation was analyzed under varying amino acid conditions.

Main Results:

• T cells exhibit macropinocytosis, which significantly increases upon activation.
• This process supports T cell growth even in amino acid-replete environments.
• Macropinocytosis facilitates extracellular amino acid uptake into endolysosomal compartments, sustaining mechanistic target of rapamycin complex 1 (mTORC1) activation.

Conclusions:

• Macropinocytosis plays a critical role in supporting T cell expansion and growth post-activation.
• The findings reveal a novel function for macropinocytosis in non-transformed mammalian cell proliferation through sustained mTORC1 activation.
• This highlights macropinocytosis as a key regulator of cell growth beyond its established role in tumor biology.