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Effect of human CD5 molecule-like (CD5L) overexpression on PMA-differentiated THP1 human monocyte-like cells

ABSTRACT: To assay the differential gene expression in human THP1-PMA differentiated macrophages expressing human CD5 molecule-like (CD5L) compared to THP1 empty vector control cells. Abstract from associated publication: Lucía Sanjurjo, Gemma Aran, Érica Téllez, Núria Amézaga, Carolina Armengol, Daniel López, Clara Prats and Maria-Rosa Sarrias. CD5L Promotes M2 Macrophage Polarization Through Autophagy-Mediated Upregulation of ID3. Frontiers in Immunology. 9:480. doi: 10.3389/fimmu.2018.00480 (2018). 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 towards 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 towards a polarization similar to that induced by IL10. Furthermore, IL10- and CD5L-treated macrophages showed increased LC3II 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 MERTK 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.

OTHER RELATED OMICS DATASETS IN: PRJNA436578

ORGANISM(S): Homo sapiens

PROVIDER: GSE111315 | GEO | 2018/03/29

REPOSITORIES: GEO

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Project description:Background: Macrophage polarization programs, commonly referred to as âclassicalâ and âalternativeâ activation, are widely considered as distinct states that are exclusive of one another, and are associated with different functions such as inflammation and wound healing, respectively. In a number of disease contexts, such as traumatic brain injury (TBI), macrophage polarization influences the extent of pathogenesis, and efforts are underway to eliminate pathogenic subsets. However, previous studies have not distinguished whether the simultaneous presence of both classical and alternative activation signatures represents the admixture of differentially polarized macrophages, or if they have adopted a unique state characterized by components of both classical and alternative activation. Results: We analyzed the polarization of individual macrophages responding to TBI using single-cell RNA sequencing. Analysis of signature polarization genes revealed diverse activation states, including M(IL4), M(IL10), and M(LPS, IFNÎ³). However, the expression of a given polarization marker was no more likely than at random to predict simultaneous expression or repression of markers of another polarization program within the same cell, suggesting a lack of exclusivity in macrophage polarization states in vivo in TBI. Also unexpectedly, individual TBI macrophages simultaneously expressed high levels of signature polarization genes across two or three different polarization states, and in several distinct and seemingly incompatible combinations. Conclusions: Single-cell gene expression profiling demonstrated that monocytic macrophages in TBI are not comprised of distinctly polarized subsets, but are uniquely and broadly activated. TBI macrophage activation in vivo is deeply complex, with individual cells concurrently adopting both inflammatory and reparative features. These data provide physiologically relevant evidence that the early macrophage response to TBI is comprised of novel activation states that are discordant with the current paradigm of macrophage polarizationâa key consideration for therapeutic modulation. Monocyte derived macrophages were isolated from the ipsilateral hemisphere of mouse brains one day following traumatic brain injury elicited by control cortical impact in C57BL/6 adult male mice. Single-cells were isolated and processed for RNA sequencing using a Fluidigm C1 integrated fluidic circuit chip. 45 biological replicates were analyzed.

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Effect of human CD5 molecule-like (CD5L) overexpression on PMA-differentiated THP1 human monocyte-like cells

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