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* Department of Medicine and Oncology, Sir Mortimer B. Davis Jewish General Hospital & Lady Davis Institute for Medical Research, McGill University, Montreal, Quebec, Canada; and
Division of Molecular and Cellular Biology, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Canada
Bone marrow-derived mesenchymal stromal cells (MSC) possess an immune plasticity manifested by either an immunosuppressive or, when activated with IFN-
, an APC phenotype. Herein, TLR expression by MSC and their immune regulatory role were investigated. We observed that human MSC and macrophages expressed TLR3 and TLR4 at comparable levels and TLR-mediated activation of MSC resulted in the production of inflammatory mediators such as IL-1β, IL-6, IL-8/CXCL8, and CCL5. IFN-
or IFN- priming up-regulated production of these inflammatory mediators and expression of IFNB, inducible NO synthase (iNOS), and TRAIL upon TLR activation in MSC and macrophages, but failed to induce IL-12 and TNF- production in MSC. Nonetheless, TLR activation in MSC resulted in the formation of an inflammatory site attracting innate immune cells, as evaluated by human neutrophil chemotaxis assays and by the analysis of immune effectors retrieved from Matrigel-embedded MSC injected into mice after in vitro preactivation with cytokines and/or TLR ligands. Hence, TLR-activated MSC are capable of recruiting immune inflammatory cells. In addition, IFN priming combined with TLR activation may increase immune responses induced by Ag-presenting MSC through presentation of Ag in an inflammatory context, a mechanism that could be applied in a cell-based vaccine.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by a Terry Fox Foundation New Frontiers Program Project Grant and by the Canadian Institute for Health Research Operating Grant MOP-15017. M.F. is a PhD candidate at McGill University and is the recipient of a Canadian Institute for Health Research Studentship and J.G. is a Fonds de Recherché en Santé du Québec Chercheur Senior.
2 R.R.-M. and M.F. contributed equally to this study.
3 Address correspondence and reprint requests to Dr. Jacques Galipeau, Department of Medicine and Oncology, Sir Mortimer B. Davis Jewish General Hospital & Lady Davis Institute for Medical Research, McGill University, 3755 Cote Sainte-Catherine Road, Montreal, Quebec, Canada H3T 1E2. E-mail address: jacques.galipeau{at}mcgill.ca
4 Abbreviations used in this paper: MSC, mesenchymal stromal cell; DC, dendritic cell; poly(I:C), polyinosinic:polycytidylic acid; mMSC, mouse MSC; hMSC, human MSC; rh, recombinant human; rm, recombinant mouse; yo, year old; PS, penicillin and streptomycin; IRF, IFN regulatory factor; iNOS, inducible NO synthase; NOS, NO synthase.
5 The online version of this article contains supplemental material.
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  M. Francois, R. Romieu-Mourez, S. Stock-Martineau, M.-N. Boivin, J. L. Bramson, and J. Galipeau Mesenchymal stromal cells cross-present soluble exogenous antigens as part of their antigen-presenting cell properties Blood, September 24, 2009; 114(13): 2632 - 2638. [Abstract] [Full Text] [PDF]
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