CD54-Mediated Interaction with Pro-inflammatory Macrophages Increases the Immunosuppressive Function of Human Mesenchymal Stromal Cells

Overview

Journal Stem Cell Reports

Publisher Cell Press

Specialty Cell Biology

Date 2017 Mar 24

PMID 28330617

Citations 54

Authors

Nicolas Espagnolle

Adelie Balguerie

Emmanuelle Arnaud

Luc Sensebe

Audrey Varin

Affiliations

Soon will be listed here.

Abstract

Mesenchymal stromal cells (MSCs) sense and modulate inflammation and represent potential clinical treatment for immune disorders. However, many details of the bidirectional interaction of MSCs and the innate immune compartment are still unsolved. Here we describe an unconventional but functional interaction between pro-inflammatory classically activated macrophages (M1MΦ) and MSCs, with CD54 playing a central role. CD54 was upregulated and enriched specifically at the contact area between M1MФ and MSCs. Moreover, the specific interaction induced calcium signaling and increased the immunosuppressive capacities of MSCs dependent on CD54 mediation. Our data demonstrate that MSCs can detect an inflammatory microenvironment via a direct and physical interaction with innate immune cells. This finding opens different perspectives for MSC-based cell therapy.

Citing Articles

Cellular crosstalk in the bone marrow niche.

Huang Z, Iqbal Z, Zhao Z, Liu J, Alabsi A, Shabbir M J Transl Med. 2024; 22(1):1096.

PMID: 39627858 PMC: 11613879. DOI: 10.1186/s12967-024-05900-6.

Epigenetic control of dental stem cells: progress and prospects in multidirectional differentiation.

Li Y, Guo X, Yao H, Zhang Z, Zhao H Epigenetics Chromatin. 2024; 17(1):37.

PMID: 39623487 PMC: 11613947. DOI: 10.1186/s13072-024-00563-5.

The Effects of the Pneumonia Lung Microenvironment on MSC Function.

Liu L, Fandino J, McCarthy S, Masterson C, Sallent I, Du S Cells. 2024; 13(18.

PMID: 39329762 PMC: 11430541. DOI: 10.3390/cells13181581.

The Myofibroblast Fate of Therapeutic Mesenchymal Stromal Cells: Regeneration, Repair, or Despair?.

Younesi F, Hinz B Int J Mol Sci. 2024; 25(16).

PMID: 39201399 PMC: 11354465. DOI: 10.3390/ijms25168712.

Neuromuscular Polytrauma Pain is Resolved by Macrophage COX-2 Nanoimmunomodulation.

Cortez I, Gaffney C, Vichare R, Crelli C, Liu L, Lee E Int J Nanomedicine. 2024; 19:7253-7271.

PMID: 39050880 PMC: 11268785. DOI: 10.2147/IJN.S460418.

References

Im G, Shin Y, Lee K . Do adipose tissue-derived mesenchymal stem cells have the same osteogenic and chondrogenic potential as bone marrow-derived cells?. Osteoarthritis Cartilage. 2005; 13(10):845-53. DOI: 10.1016/j.joca.2005.05.005. View

Phinney D, Di Giuseppe M, Njah J, Sala E, Shiva S, St Croix C . Mesenchymal stem cells use extracellular vesicles to outsource mitophagy and shuttle microRNAs. Nat Commun. 2015; 6:8472. PMC: 4598952. DOI: 10.1038/ncomms9472. View

Kern S, Eichler H, Stoeve J, Kluter H, Bieback K . Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells. 2006; 24(5):1294-301. DOI: 10.1634/stemcells.2005-0342. View

ZuK P, Zhu M, Ashjian P, De Ugarte D, Huang J, Mizuno H . Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell. 2002; 13(12):4279-95. PMC: 138633. DOI: 10.1091/mbc.e02-02-0105. View

Ren G, Su J, Zhang L, Zhao X, Ling W, Lhuillie A . Species variation in the mechanisms of mesenchymal stem cell-mediated immunosuppression. Stem Cells. 2009; 27(8):1954-62. DOI: 10.1002/stem.118. View

Francois M, Romieu-Mourez R, Li M, Galipeau J . Human MSC suppression correlates with cytokine induction of indoleamine 2,3-dioxygenase and bystander M2 macrophage differentiation. Mol Ther. 2011; 20(1):187-95. DOI: 10.1038/mt.2011.189. View

Duffy M, Ritter T, Ceredig R, Griffin M . Mesenchymal stem cell effects on T-cell effector pathways. Stem Cell Res Ther. 2011; 2(4):34. PMC: 3219065. DOI: 10.1186/scrt75. View

Waterman R, Tomchuck S, Henkle S, Betancourt A . A new mesenchymal stem cell (MSC) paradigm: polarization into a pro-inflammatory MSC1 or an Immunosuppressive MSC2 phenotype. PLoS One. 2010; 5(4):e10088. PMC: 2859930. DOI: 10.1371/journal.pone.0010088. View

Rasmusson I, Ringden O, Sundberg B, Le Blanc K . Mesenchymal stem cells inhibit the formation of cytotoxic T lymphocytes, but not activated cytotoxic T lymphocytes or natural killer cells. Transplantation. 2003; 76(8):1208-13. DOI: 10.1097/01.TP.0000082540.43730.80. View

10.

Grakoui A, Bromley S, Sumen C, Davis M, Shaw A, Allen P . The immunological synapse: a molecular machine controlling T cell activation. Science. 1999; 285(5425):221-7. DOI: 10.1126/science.285.5425.221. View

11.

Roozendaal R, Mebius R . Stromal cell-immune cell interactions. Annu Rev Immunol. 2010; 29:23-43. DOI: 10.1146/annurev-immunol-031210-101357. View

12.

Crisan M, Yap S, Casteilla L, Chen C, Corselli M, Park T . A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell. 2008; 3(3):301-13. DOI: 10.1016/j.stem.2008.07.003. View

13.

Spaggiari G, Abdelrazik H, Becchetti F, Moretta L . MSCs inhibit monocyte-derived DC maturation and function by selectively interfering with the generation of immature DCs: central role of MSC-derived prostaglandin E2. Blood. 2009; 113(26):6576-83. DOI: 10.1182/blood-2009-02-203943. View

14.

Freytes D, Kang J, Marcos-Campos I, Vunjak-Novakovic G . Macrophages modulate the viability and growth of human mesenchymal stem cells. J Cell Biochem. 2012; 114(1):220-9. DOI: 10.1002/jcb.24357. View

15.

Le Blanc K, Rasmusson I, Sundberg B, Gotherstrom C, Hassan M, Uzunel M . Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet. 2004; 363(9419):1439-41. DOI: 10.1016/S0140-6736(04)16104-7. View

16.

Polchert D, Sobinsky J, Douglas G, Kidd M, Moadsiri A, Reina E . IFN-gamma activation of mesenchymal stem cells for treatment and prevention of graft versus host disease. Eur J Immunol. 2008; 38(6):1745-55. PMC: 3021120. DOI: 10.1002/eji.200738129. View

17.

Roebuck K, Finnegan A . Regulation of intercellular adhesion molecule-1 (CD54) gene expression. J Leukoc Biol. 1999; 66(6):876-88. DOI: 10.1002/jlb.66.6.876. View

18.

Prockop D . Concise review: two negative feedback loops place mesenchymal stem/stromal cells at the center of early regulators of inflammation. Stem Cells. 2013; 31(10):2042-6. DOI: 10.1002/stem.1400. View

19.

Horwitz E, Prockop D, Fitzpatrick L, Koo W, Gordon P, Neel M . Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta. Nat Med. 1999; 5(3):309-13. DOI: 10.1038/6529. View

20.

Selmani Z, Naji A, Zidi I, Favier B, Gaiffe E, Obert L . Human leukocyte antigen-G5 secretion by human mesenchymal stem cells is required to suppress T lymphocyte and natural killer function and to induce CD4+CD25highFOXP3+ regulatory T cells. Stem Cells. 2007; 26(1):212-22. DOI: 10.1634/stemcells.2007-0554. View