Peripheral blood mononuclear cell response to YKL-40 and Galectin-3 in cystic fibrosis

Cytokine. 2021 Oct:146:155635. doi: 10.1016/j.cyto.2021.155635. Epub 2021 Jul 15.


Background: Elevated circulating levels of YKL-40 correlate with disease severity in Cystic Fibrosis (CF), but the role of YKL-40 in the inflammatory response in CF is still under investigation. Our main goal was to evaluate if YKL-40 can modulate the expression of major cytokines (IL-6, IL-10, IL-13) implicated in the inflammatory response in CF. A secondary goal was to explore the interactions between YKL-40 and other circulating proteins to determine the impacts on cytokine modulation.

Method: Peripheral blood mononuclear cells (PBMCs) were isolated from the blood of 83 adult CF patients in stable clinical condition. PBMCs were treated with human YKL-40 followed by the measure of IL-6, IL-10 and IL-13 gene expression. Protein arrays were used to explore the interactions between YKL-40 and circulating proteins. Interaction with Galectin-3 (GAL3) was identified, and confirmed by binding assay. Cytokine gene expressions were again monitored by RT-qPCR after PBMC treatment with GAL3, with or without YKL-40 co-stimulation.

Results: Following YKL-40 stimulation, PBMC gene expression of IL-6, IL-10 and IL-13 varies across patients. IL-6 and IL-13 are coexpressed, but this response was different in male and female patients. GAL3 protein was detected in the blood of CF patients, and a molecular interaction with YKL-40 was identified. GAL3 did not interfere with the YKL-40 stimulation of IL-6, IL-10 and IL-13 but may modulate the coexpression.

Conclusion: We observed that YKL-40 stimulation had a variable impact on IL-6, IL-10, and IL-13 gene expression in CF PBMCs and uncovered an interaction between GAL3 and YKL-40 in the serum of CF patients. Our findings suggest that YKL-40 is not only a biomarker of disease severity in CF, but it might play an active role in the inflammatory pathophysiology of the disease.

Keywords: Cystic fibrosis; Galectin; IL10; IL13; IL6; Peripherical blood mononuclear cells; YKL-40.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Chitinase-3-Like Protein 1 / blood*
  • Cystic Fibrosis / blood*
  • Cytokines / metabolism
  • Female
  • Galectin 3 / blood*
  • Humans
  • Inflammation Mediators / metabolism
  • Leukocytes, Mononuclear / metabolism*
  • Male
  • Protein Binding


  • CHI3L1 protein, human
  • Chitinase-3-Like Protein 1
  • Cytokines
  • Galectin 3
  • Inflammation Mediators