Related Experiment Video

Updated: Apr 5, 2026

Mechanistic Insight into the Development of TNBS-Mediated Intestinal Fibrosis and Evaluating the Inhibitory Effects of Rapamycin
10:21

Mechanistic Insight into the Development of TNBS-Mediated Intestinal Fibrosis and Evaluating the Inhibitory Effects of Rapamycin

Published on: September 12, 2019

7.9K

Legumain Restrains Granuloma Formation by Inhibiting mTORC1/STAT1-Mediated M1 Macrophage Polarization in Sarcoidosis

Mengyuan Liu1,2,3, Yueyin Han1,2,3, Bingbing Xie2,3

  • 1China-Japan Friendship Hospital (Institute of Clinical Medical Sciences), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|April 4, 2026
PubMed

Insights

Legumain (LGMN) restrains sarcoid granuloma formation by inhibiting M1 macrophage polarization. LGMN supplementation shows promise as a novel therapeutic strategy for treating sarcoidosis.

Area of Science:

  • Immunology
  • Cell Biology

Background:

  • Sarcoidosis is a systemic granulomatous disease with limited treatment options.
  • Macrophages are crucial in sarcoid granuloma initiation.
  • Legumain (LGMN), a cysteine protease, regulates macrophage polarization in cancer, but its role in sarcoidosis is unknown.

Purpose of the Study:

  • To investigate the role of LGMN in sarcoid granuloma formation.
  • To elucidate the mechanism by which LGMN affects macrophage polarization in sarcoidosis.
  • To evaluate LGMN as a potential therapeutic target for sarcoidosis.

Main Methods:

  • Investigated LGMN expression in a mouse model of sarcoid-like granulomas.
  • Utilized genetic deletion of Lgmn in a Propionibacterium acnes (P. acnes)-induced mouse model.
  • Examined the effect of LGMN on macrophage polarization (M1/M2) and the mTORC1/STAT1 pathway.
  • Administered Lgmn plasmid DNA via lipid nanoparticles in vivo to assess therapeutic potential.

Main Results:

  • LGMN was upregulated in macrophages within sarcoid-like granulomas.
  • Genetic deletion of Lgmn exacerbated granulomatous inflammation and increased M1 macrophage polarization.
  • LGMN binds to integrin αvβ3, inhibiting the mTORC1/STAT1 pathway and M1 polarization.
  • Intratracheal delivery of Lgmn alleviated granuloma formation and reduced M1 polarization.

Conclusions:

  • LGMN plays a critical role in suppressing sarcoid granulomatous inflammation.
  • LGMN restrains M1 macrophage polarization via the mTORC1/STAT1 pathway.
  • LGMN supplementation represents a potential therapeutic strategy for sarcoidosis.
Keywords:
granulomaslegumainlipid nanoparticlesmacrophagessarcoidosis

More Related Videos

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity07:09

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity

Published on: January 7, 2019

8.1K

Related Concept Videos

The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
14.0K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
5.1K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
6.4K