title: Inflammation modifies the pattern and the function of Toll-like receptors expressed by human mesenchymal stromal cells.
abstract: Mesenchymal stromal cells (MSC) are involved in tissue repair and in the regulation of immune responses. MSC express Toll-like receptors (TLR) known to link innate and adaptive immunity. We hypothesized that TLR signaling could influence human MSC (hMSC) function. Here, we show that hMSC express TLR1, TLR2, TLR3, TLR4, TLR5, and TLR6 but not TLR7, TLR8, TLR9, and TLR10. In inflammatory conditions mimicked by culturing hMSC in an inflammatory environment, TLR2, TLR3, and TLR4 are upregulated, whereas TLR6 is downregulated. Interleukin (IL)-1 beta, IL-6, IL-12p35 and transforming growth factor-beta mRNAs are constitutively expressed by hMSC. Inflammation leads to an increase in IL-1 beta, IL-6, IL-12p35, and transforming growth factor-beta transcription and is characterized by IL-23p19 and IL-27p28 transcription. In this setting, poly(I:C) further augments IL-6, IL-12p35, IL-23p19, and IL-27p28 transcription, whereas lipopolysaccharide (LPS) increases IL-23p19 and IL-27p28 transcription. By upregulating TLR3 and TLR4 transcription, inflammation increases the hMSC responsiveness to LPS and poly(I:C), leading to a proinflammatory shift in their cytokine profile. The hMSC osteogenic potential does not change after TLR triggering but stimulation with LPS and poly(I:C) results in a decrease in their immunosuppressive capabilities. In conclusion, TLR activation in hMSC may affect their function and could modify their in vivo fate, especially in an inflammatory context.
authors.affiliation: Laboratory of Experimental Hematology, Institut Jules Bordet, Université Libre de Bruxelles, Bruxelles, Brussels, Belgium. gordana30@yahoo.com
authors.forename: Gordana
authors.initials: G
authors.lastname: Raicevic
authors.forename: Redouane
authors.initials: R
authors.lastname: Rouas
authors.forename: Mehdi
authors.initials: M
authors.lastname: Najar
authors.forename: Patrick
authors.initials: P
authors.lastname: Stordeur
authors.forename: Hicham Id
authors.initials: HI
authors.lastname: Boufker
authors.forename: Dominique
authors.initials: D
authors.lastname: Bron
authors.forename: Philippe
authors.initials: P
authors.lastname: Martiat
authors.forename: Michel
authors.initials: M
authors.lastname: Goldman
authors.forename: Michel T
authors.initials: MT
authors.lastname: Nevessignsky
authors.forename: Laurence
authors.initials: L
authors.lastname: Lagneaux
mesh_terms: D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D007249:Inflammation; D008070:Lipopolysaccharides / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D011070:Poly I-C / Q000494:pharmacology; D017154:Stromal Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051193:Toll-Like Receptors / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D051193:Toll-Like Receptors; D011070:Poly I-C