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Published on: January 7, 2019

mTORC1-Dependent Regulation of the CCL24-CCR3 Axis Controls Granuloma Formation and Maintenance in Sarcoidosis

Xiongjian Rao1,2, Jinpeng Liu2, Derek B Allison2

  • 1Department of Toxicology and Cancer Biology, University of Kentucky, Lexington, Kentucky, USA.

Molecular and Cellular Biology
|June 5, 2026
PubMed

Insights

Scientists discovered that blocking the mTORC1 pathway in mice triggers sarcoidosis-like granulomas. This pathway affects CCL24-CCR3 signaling, a potential target for treating this inflammatory disease.

Area of Science:

  • Immunology
  • Molecular Biology
  • Pathology

Background:

  • Sarcoidosis is a chronic inflammatory disease characterized by granulomas, but its molecular causes are not fully understood.
  • This lack of understanding impedes the development of targeted therapies for sarcoidosis.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying sarcoidosis pathogenesis.
  • To identify potential therapeutic targets for sarcoidosis.

Main Methods:

  • A murine model with Tsc1/Tsc2 deletion in fibroblasts and macrophages was used to induce sarcoid-like granulomas.
  • Inflammatory cytokine/chemokine arrays were employed to identify key immunoregulatory molecules.
  • The role of the mTORC1 pathway and its downstream signaling in granuloma formation was examined.
  • Pharmacological interventions (rapamycin, azithromycin) were tested for their therapeutic effects.

Main Results:

  • Hyperactivation of the mTORC1 pathway in fibroblasts and macrophages led to spontaneous sarcoid-like granuloma formation in mice.
  • CCL24, a chemokine ligand for CCR3, was found to be downregulated in the murine model and human sarcoidosis patients.
  • mTORC1 was shown to suppress CCL24 expression via STAT3 signaling and promote CCR3 expression in macrophages, establishing a novel regulatory axis.
  • Rapamycin and azithromycin treatment reduced granuloma burden and normalized CCL24-CCR3 signaling.

Conclusions:

  • The study establishes a mechanistic link between mTORC1 pathway activation, CCL24-CCR3 signaling dysregulation, and sarcoidosis pathogenesis.
  • This research provides new insights into the molecular basis of sarcoidosis.
  • The identified mTORC1-CCL24-CCR3 axis presents promising therapeutic targets for sarcoidosis intervention.
Keywords:
CCL24-CCR3inflammationmTORsarcoidosis

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