Extracellular vesicles mediate intercellular communication: Transfer of functionally active microRNAs by...

Area of Science:

• Immunology
• Molecular Biology
• Cell Biology

Background:

• Extracellular vesicles (EVs), such as exosomes and microvesicles (MVs), are released during cell activation and apoptosis.
• EVs, particularly MVs, are implicated in immune modulation and autoimmune disease pathogenesis, with a known capacity to carry microRNAs (miRNAs).

Purpose of the Study:

• To systematically characterize MVs and exosomes based on their release stimuli.
• To analyze the miRNA content of viable or apoptotic human T lymphocytes and their corresponding MVs.
• To investigate the functional impact of EV engulfment on human monocytes and compare miRNA expression in T lymphocytes and MVs between healthy individuals and systemic lupus erythematosus (SLE) patients.

Main Methods:

• Systematic characterization of MVs and exosomes based on release stimuli.
• Analysis of miRNA content in viable or apoptotic human T lymphocytes and released MVs.
• Measurement of miRNA, protein, surface marker expression, and cytokine release in human monocytes after EV engulfment.
• Comparative analysis of miRNA expression in T lymphocytes and MVs from healthy individuals and SLE patients.

Main Results:

• Distinct EV subtypes were released depending on the stimuli, differing in size and RNA profiles.
• Apoptosis induction led to the accumulation of specific miRNAs in MVs, which were functionally transferred to human monocytes.
• MVs from apoptotic cells induced a less inflammatory response in monocytes compared to those from viable cells.
• Specific miRNAs (miR-155*, miR-34b, miR-34a) were deregulated in T lymphocytes and MVs of SLE patients compared to healthy individuals.

Conclusions:

• EV release is stimulus-dependent, yielding distinct subtypes with specific RNA cargo.
• MVs mediate functional miRNA transfer and can modulate monocyte inflammatory responses.
• Aberrant miRNA expression in T lymphocytes and MVs is associated with systemic lupus erythematosus, suggesting a role in disease pathogenesis.