Inflammation modifies the pattern and the function of Toll-like receptors expressed by human mesenchymal stromal cells.
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.
Raicevic
Gordana
G
Laboratory of Experimental Hematology, Institut Jules Bordet, Université Libre de Bruxelles, Bruxelles, Brussels, Belgium. gordana30@yahoo.com
Rouas
Redouane
R
Najar
Mehdi
M
Stordeur
Patrick
P
Boufker
Hicham Id
HI
Bron
Dominique
D
Martiat
Philippe
P
Goldman
Michel
M
Nevessignsky
Michel T
MT
Lagneaux
Laurence
L
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
D016207:Cytokines; D008070:Lipopolysaccharides; D051193:Toll-Like Receptors; D011070:Poly I-C