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Polymerized Type I Collagen Downregulates STAT-1 Phosphorylation Through Engagement with LAIR-1 in Circulating

Elizabeth Olivares-Martínez1, Diego Francisco Hernández-Ramírez1, Carlos Alberto Núñez-Álvarez1

  • 1Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, Mexico.

International Journal of Molecular Sciences
|February 13, 2025
PubMed

Insights

Polymerized type I collagen (PTIC) treatment reduced inflammation and improved symptoms in COVID-19 patients by acting as a LAIR1 agonist. This therapy downregulates STAT1 phosphorylation, offering potential for inflammatory diseases like COVID-19 and long COVID.

Area of Science:

  • Immunology
  • Molecular Biology
  • Virology

Background:

  • Symptomatic COVID-19 involves hyperinflammation.
  • Polymerized type I collagen (PTIC) shows potential for treating COVID-19.
  • LAIR1 is a suspected receptor for PTIC.

Purpose of the Study:

  • To investigate the interaction between PTIC and LAIR1.
  • To determine PTIC's effect on inflammatory pathways, specifically STAT1 phosphorylation.
  • To evaluate PTIC's clinical efficacy in COVID-19 outpatients.

Main Methods:

  • Binding assays (SPR) to assess PTIC-LAIR1 affinity.
  • Western blot analysis of inflammatory markers (NF-κB, p38, STAT1) in macrophages.
  • Flow cytometry and luminometry to measure monocyte subsets and serum cytokines in patients.

Main Results:

  • PTIC demonstrated binding affinity to LAIR1, similar to collagen.
  • PTIC downregulated STAT1 phosphorylation in IFN-γ-induced M1 macrophages.
  • COVID-19 patients treated with PTIC showed reduced pro-inflammatory cytokines and Mo1 subset, correlating with symptom improvement.

Conclusions:

  • PTIC acts as a LAIR1 agonist, downregulating STAT1 phosphorylation.
  • PTIC effectively reduces inflammation and improves clinical outcomes in COVID-19 patients.
  • PTIC holds promise for treating STAT1-mediated inflammatory conditions, including COVID-19 and long COVID.

Keywords:
LAIR1M1 macrophagesMo1 monocytesSTAT1long COVIDpolymerized type I collagen

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