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Title

Folate Receptor β (FRβ) Expression in Tissue-Resident and Tumor-Associated Macrophages Associates with and Depends on the Expression of PU.1

AuthorsSamaniego, Rafael ; Domínguez-Soto, Ángeles ; Ratnam, Manohar; Matsuyama, Takami; Sánchez-Mateos, Paloma; Corbí, Angel L. ; Puig-Kröger, Amaya
KeywordsMacrophages
Inflammation
Rheumatoid arthritis
Tumor-associated macrophages
Folate receptor
Issue Date2020
PublisherMultidisciplinary Digital Publishing Institute
CitationCells 9(6): 1445 (2020)
AbstractAs macrophages exhibit a huge functional plasticity under homeostasis and pathological conditions, they have become a therapeutic target for chronic inflammatory diseases. Hence, the identification of macrophage subset-specific markers is a requisite for the development of macrophage-directed therapeutic interventions. In this regard, the macrophage-specific Folate Receptor β (FRβ, encoded by the FOLR2 gene) has been already validated as a target for molecular delivery in cancer as well as in macrophage-targeting therapeutic strategies for chronic inflammatory pathologies. We now show that the transcriptome of human macrophages from healthy and inflamed tissues (tumor; rheumatoid arthritis, RA) share a significant over-representation of the “anti-inflammatory gene set”, which defines the gene profile of M-CSF-dependent IL-10-producing human macrophages (M-MØ). More specifically, FOLR2 expression has been found to strongly correlate with the expression of M-MØ-specific genes in tissue-resident macrophages, tumor-associated macrophages (TAM) and macrophages from inflamed synovium, and also correlates with the presence of the PU.1 transcription factor. In fact, PU.1-binding elements are found upstream of the first exon of FOLR2 and most M-MØ-specific- and TAM-specific genes. The functional relevance of PU.1 binding was demonstrated through analysis of the proximal regulatory region of the FOLR2 gene, whose activity was dependent on a cluster of PU.1-binding sequences. Further, siRNA-mediated knockdown established the importance of PU.1 for FOLR2 gene expression in myeloid cells. Therefore, we provide evidence that FRβ marks tissue-resident macrophages as well as macrophages within inflamed tissues, and its expression is dependent on PU.1.
Description© 2020 by the authors.
Publisher version (URL)https://doi.org/10.3390/cells9061445
URIhttp://hdl.handle.net/10261/215657
DOIhttp://dx.doi.org/10.3390/cells9061445
ISSN2073-4409
E-ISSN2073-4409
Appears in Collections:(CIB) Artículos
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