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BLOC1S1 regulates autolysosomal and exosomal dynamics during CD4+ T cell differentiation

Rahul Sharma1, Zulfeqhar A Syed2, Sandeep K Vishwakarma3

  • 1Laboratory of Mitochondrial Biology and Metabolism, NHLBI, NIH, Bethesda, Maryland, USA.

Biorxiv : the Preprint Server for Biology
|June 4, 2026
PubMed

Insights

BLOC1S1 deficiency in CD4+ T cells disrupts lysosomal function, increasing exocytosis and promoting Th2 immunity. This highlights BLOC1S1

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • The endolysosome system is vital for cellular processes.
  • Its role in immune regulation, particularly T helper 2 (Th2) immunity, is not fully understood.
  • BLOC1S1 is a protein complex involved in endolysosomal trafficking.

Purpose of the Study:

  • To investigate the role of BLOC1S1 in CD4+ T cell function.
  • To explore the link between endolysosomal dynamics and Th2 immune responses.
  • To understand how BLOC1S1 deficiency impacts T cell signaling and cytokine secretion.

Main Methods:

  • CD4+ T cell-specific depletion of BLOC1S1 in a mouse model.
  • Analysis of lysosomal distribution and endosomal vesicle accumulation.
  • Assessment of exocytosis and exosome production.
  • siRNA knockdown of RAB11 and VAMP7 to inhibit vesicle trafficking.
  • Measurement of Th2 cytokine secretion.
  • In vitro experiments using exosomes from BLOC1S1-deficient T cells.

Main Results:

  • BLOC1S1 deficiency in CD4+ T cells led to aberrant lysosomal distribution and increased endosomal vesicles.
  • This correlated with enhanced Th2 immune responses and increased exocytosis.
  • Upregulation of exocytosis machinery proteins (RAB11, VAMP7) was observed.
  • siRNA knockdown of RAB11 and VAMP7 reduced Th2 cytokine secretion in BLOC1S1-deficient cells.
  • Exosomes from BLOC1S1-deficient T cells promoted Th2 polarization in recipient cells.

Conclusions:

  • BLOC1S1 is a critical regulator of lysosomal dynamics and exocytic vesicle fusion in CD4+ T cells.
  • Intracellular trafficking mechanisms controlled by BLOC1S1 are essential for Th2 immune regulation.
  • BLOC1S1 deficiency enhances Th2 immunity through altered exosome-mediated cytokine export and amplification.

Keywords:
BLOC1S1CD4+ T cellsTh2 polarizationcytokine secretionendolysosomal traffickingexosomes

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