CD105 Deficiency in Mouse Aorta-Derived Progenitor Cells Promotes an Enhanced Inflammatory Response to Lipopolysaccharide

Abstract

2015). The phenotypic characteristics associated with these properties are an active area of study and their expression of toll-like receptors (TLR) are thought to play a role. TLR transmembrane protein receptors are sensors of microorganisms and have a critical function in innate immunity (Waterman, Tomchuck, Henkle, & Betancourt, 2010). Many studies have also focused on the role of surface antigens. The surface antigens CD73, CD90 and CD105 are used to identify mesenchymal progenitors (Dominici et al., 2006), but also are likely to participate in their regulation of immune cells. Previous research groups have reported that mesenchymal progenitors derived from mouse aorta (mAo) highly express CD90 and CD105, but do not express CD73 (Fernandez et al., 2017). This population of mesenchymal progenitors (mAo), when in coculture with macrophages, promotes inflammation (Evans et al., 2015). In contrast, a mouse bone marrow derived cell line lacking expression of CD90 and CD105 suppresses macrophage activity (Fernandez et al., 2017). The mechanisms mediating this opposing regulation are yet to be determined but because CD105 is highly expressed in chronically inflamed tissues (Middleton et al., 2005), our goal was to focus on its role in the mAo’s ability to support the macrophage inflammatory response. CD105 or endoglin is a co-receptor for the TGFβ superfamily of receptors. TGFβ receptors are known for their function in regulating cell growth and differentiation of cells (Lin & Moustakas, 1994). Due to alternative splicing of the CD105 transcript, there is both a long isoform (L-CD105) and short isoform (S-CD105) of the CD105 protein (Dallas et al., 2008). The two isoforms share identical sequences (Bellon et al., 1993; Gougos & Letarte, 1990); however, L-CD105 contains an extra sequence leading to funcINTRODUCTION The development and use of cell-based therapeutics is at the forefront of modern medicine, and mesenchymal progenitor cells are a major focus of investigation. Mesenchymal progenitor cells are the multipotent precursors to connective tissue cells (Young et al., 1995) and have traditionally been studied due to their role in tissue repair after damage. They are also capable of regulating immune cell function through direct and indirect cell contact making them a novel tool in the treatment of many inflammatory diseases (Aggarwal & Pittenger, 2005). They can modulate the activity of many immune cell types including macrophages and can be immunosupportive or immunosuppressive. Some mesenchymal progenitors influence macrophages by alternating their orientation from the inflammatory M1 to the anti-inflammatory M2 phenotype, rendering these progenitors immunosuppressive (Cho et al., 2014; Fernandez et al., 2017). Other studies show that mesenchymal progenitors are pro-inflammatory when co-cultured with macrophages making these progenitors immunosupportive (Anton, Banerjee, & Glod, 2012; Evans, Salvador, George, Trevino-Gutierrez, & Nunez, CD105 Deficiency in Mouse Aorta-Derived Progenitor Cells Promotes an Enhanced Inflammatory Response to Lipopolysaccharide