CD5L Promotes M2 Macrophage Polarization through Autophagy-Mediated Upregulation of ID3

Abstract

CD5L (CD5 molecule-like) is a secreted glycoprotein that controls key mechanisms in inflammatory responses, with involvement in processes such as infection, atherosclerosis, and cancer. In macrophages, CD5L promotes an anti-inflammatory cytokine profile in response to TLR activation. In the present study, we questioned whether CD5L is able to influence human macrophage plasticity, and drive its polarization toward any specific phenotype. We compared CD5L-induced phenotypic and functional changes to those caused by IFN/LPS, IL4, and IL10 in human monocytes. Phenotypic markers were quantified by RT-qPCR and flow cytometry, and a mathematical algorithm was built for their analysis. Moreover, we compared ROS production, phagocytic capacity, and inflammatory responses to LPS. CD5L drove cells toward a polarization similar to that induced by IL10. Furthermore, IL10- and CD5L-treated macrophages showed increased LC3-II content and colocalization with acidic compartments, thereby pointing to the enhancement of autophagy-dependent processes. Accordingly, siRNA targeting ATG7 in THP1 cells blocked CD5L-induced CD163 and Mer tyrosine kinase mRNA and efferocytosis. In these cells, gene expression profiling and validation indicated the upregulation of the transcription factor ID3 by CD5L through ATG7. In agreement, ID3 silencing reversed polarization by CD5L. Our data point to a significant contribution of CD5L-mediated autophagy to the induction of ID3 and provide the first evidence that CD5L drives macrophage polarization.

CD5L‑induced activation of autophagy is associated with hepatoprotection in ischemic reperfusion injury via the CD36/ATG7 axis

“…The results of the present study demonstrated that I/R induced ROS generation and inhibited antioxidative enzyme activity. A previous study has suggested that CD5L induces anti-inflammatory effects by autophagy (20); therefore, the inhibitory effect of CD5L on oxidative stress was examined in the present study. In accordance with the result of previous study, CD5L inhibited the oxidative stress induced by I/R.…”

“…CD5L is a 40-kDa soluble glycoprotein that belongs to the scavenger receptor cysteine rich superfamily (32). CD5L is involved in a variety of biological processes, such as infection, atherosclerosis and apoptosis (11,20). Various disease models, including cancer, have demonstrated that CD5L participates in cellular functions by preventing apoptosis (33,34).…”

“…During ischemia, the absence of oxygen leads to an accumulation of ROS and a reduction in antioxidative enzymes (19). A previous study has suggested that CD5L may promote an anti-inflammatory cytokine profile through the modulation of autophagy, leading to an inhibition of ROS generation (20). The present study investigated whether CD5L was able to modulate cellular oxidative stress to alleviate the I/R injury.…”

Early Treatment of Interleukin-33 Can Attenuate Lupus Development in Young NZB/W F1 Mice

“…The top genes that were upregulated upon IL-33 administration were retnla/Fizz1, Arg1, rnase2, CD5L, prg2, saa3, chil3, and alox15. Interestingly, these genes have been widely implicated in the development of the suppressive, alternatively activated M2 macrophages [28][29][30][31][32]. Therefore, this finding implicates that IL-33 may contribute to the resolution of inflammation partly by upregulating M2-associated markers and polarization.…”

Bacterial DNA induces the formation of heat-resistant disease-associated “Tetz-proteins” in human plasma

“…For example, C4BP, CHD7, and KLK2 are known as tumour biomarkers, while CD5L, EIF5A1, FINC, and SEPP1 are not only described as biomarkers but also known to participate in tumour progression [31, 33, 57, 81].…”