Sarcoidosis and the mTOR, Rac1, and Autophagy Triad

Trends Immunol. 2020 Apr;41(4):286-299. doi: 10.1016/ Epub 2020 Feb 28.


Sarcoidosis is an enigmatic multisystem disease characterized by the development and accumulation of granulomas: a compact collection of macrophages that have differentiated into epithelioid cells and which are associated with T helper (Th)1 and Th17 cells. Although no single causative factor has been shown to underlie sarcoidosis in humans, its etiology has been related to microbial, environmental, and genetic factors. We examine how these factors play a role in sarcoidosis pathogenesis. Specifically, we propose that dysfunction of mTOR, Rac1, and autophagy-related pathways not only hampers pathogen or nonorganic particle clearance but also participates in T cell and macrophage dysfunction, driving granuloma formation. This concept opens new avenues for potentially treating sarcoidosis and may serve as a blueprint for other granulomatous disorders.

Keywords: Rac1; T cell; Treg; autophagy; azathioprine; genetics; granuloma; mTOR; monocyte; multinucleated giant cell; rapamycin; sarcoidosis; whole-exome sequencing.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Autophagy* / genetics
  • Humans
  • Macrophages / immunology
  • Macrophages / pathology
  • Sarcoidosis* / genetics
  • Sarcoidosis* / immunology
  • TOR Serine-Threonine Kinases* / immunology
  • Th1 Cells / immunology
  • Th1 Cells / pathology
  • Th17 Cells / immunology
  • rac1 GTP-Binding Protein* / immunology


  • RAC1 protein, human
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • rac1 GTP-Binding Protein