Human fibroblasts share immunosuppressive properties with bone marrow mesenchymal stem cells.
BACKGROUND
Bone marrow mesenchymal stem cells (BM-MSCs) and adipose tissue-derived stem cells share immunosuppressive capacities, suggesting that the latter could be a general property of stromal cells.


METHODS
To check this hypothesis, we compared human BM-MSC and fibroblasts for their in vitro multi-potentiality, expandability and their immunomodulatory properties under normalized optimized culture conditions.


RESULTS
We report that, unlike BM-MSCs, fibroblasts cannot differentiate in vitro into adipocytes and osteoblasts and differ from BM-MSCs by the expression of membrane CD106, CD10 and CD26 and by the expression of collagen VII mRNA. Like BM-MSCs, fibroblasts are unable to provoke in vitro allogeneic reactions, but strongly suppress lymphocyte proliferation induced by allogeneic mixed lymphocyte culture (MLC) or mitogens. We show that fibroblasts' immunosuppressive capacity is independent from prostaglandin E2, IL-10 and the tryptophan catabolising enzyme indoleamine 2,3-dioxygenase and is not abrogated after the depletion of CD8+ T lymphocytes, NK cells and monocytes.


CONCLUSIONS
Finally, fibroblasts and BM-MSCs act at an early stage through blockage of lymphocyte activation, as demonstrated by down-regulation of GZMB (granzyme B) and IL2RA (CD25) expression.
Cappellesso-Fleury
Sandrine
S
Etablissement Français du sang Pyrénées-Méditerranée, Toulouse, France.
Puissant-Lubrano
Bénédicte
B
Apoil
Pol-André
PA
Titeux
Matthias
M
Winterton
Peter
P
Casteilla
Louis
L
Bourin
Philippe
P
Blancher
Antoine
A
D000273:Adipose Tissue / Q000166:cytology; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D015536:Down-Regulation / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology / Q000276:immunology*; D053804:Granzymes / Q000235:genetics; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics; D008213:Lymphocyte Activation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology*; D017154:Stromal Cells / Q000276:immunology
C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D053804:Granzymes
J Immunol. 2007 Jan 15;178(2):1151-7
17202379
J Mol Cell Cardiol. 2001 Dec;33(12):2121-33
11735259
Stem Cells. 2006 Nov;24(11):2466-77
17071860
Exp Cell Res. 2005 Apr 15;305(1):33-41
15777785
Br J Haematol. 2005 Apr;129(1):118-29
15801964
Biochem Soc Trans. 2000;28(4):341-5
10961915
Transplantation. 1994 Jun 15;57(11):1638-42
8009598
Tissue Eng. 2007 Jan;13(1):111-21
17518585
Stem Cells. 2006 May;24(5):1294-301
16410387
Exp Hematol. 2004 May;32(5):414-25
15145209
Arthritis Res Ther. 2007;9(1):301
17284303
J Invest Dermatol. 2004 Apr;122(4):953-64
15102086
Exp Hematol. 2005 Aug;33(8):928-34
16038786
Cell Stem Cell. 2008 Feb 7;2(2):141-50
18371435
Tissue Eng. 2002 Dec;8(6):901-10
12542936
J Immunol. 2007 Sep 1;179(5):2824-31
17709496
Scand J Immunol. 2004 Sep;60(3):307-15
15320889
Wound Repair Regen. 2003 Sep-Oct;11(5):337-45
12950637
J Dermatol Sci. 2004 Dec;36(3):157-64
15541637
J Immunol. 2000 Apr 1;164(7):3596-9
10725715
Immunology. 1992 Jun;76(2):344-7
1634256
J Clin Oncol. 2000 Jan;18(2):307-16
10637244
Bone Marrow Transplant. 2004 Mar;33(6):597-604
14716336
J Cell Biochem. 2003 Sep 1;90(1):206-17
12938169
Exp Eye Res. 1993 Feb;56(2):157-65
8462649
Gene Expr. 2005;12(4-6):245-57
16355723
Gene Ther. 2003 May;10(10):928-31
12732877
Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3213-8
10725391
J Immunol. 1985 Dec;135(6):3750-62
3934267
Exp Hematol. 2000 Aug;28(8):875-84
10989188
Stem Cells. 2005 Aug;23(7):1012-20
15941858
Blood. 2002 May 15;99(10):3838-43
11986244
Haematologica. 2006 Mar;91(3):364-8
16531259
Blood. 2007 Jan 1;109(1):228-34
16985180
Rheumatology (Oxford). 1999 Dec;38(12):1203-7
10587546
J Immunol. 2007 Aug 1;179(3):1595-604
17641026
Exp Hematol. 2002 Jan;30(1):42-8
11823036
Science. 1999 Apr 2;284(5411):143-7
10102814
J Interferon Cytokine Res. 1998 Jul;18(7):509-20
9712367
J Immunol. 1987 Jan 15;138(2):385-92
3098840
Blood. 1980 Aug;56(2):289-301
6994839
Hum Mutat. 2008 Feb;29(2):267-76
18030675
Blood. 2005 Feb 15;105(4):1815-22
15494428
Prog Clin Biol Res. 1984;154:209-36
6382294
Blood. 2005 Apr 1;105(7):2821-7
15591115
Exp Hematol. 2005 Nov;33(11):1402-16
16263424
J Immunol. 2003 Oct 1;171(7):3426-34
14500637
Cell Tissue Kinet. 1970 Oct;3(4):393-403
5523063
Exp Cell Res. 2006 Jul 15;312(12):2169-79
16631737
Bone Marrow Transplant. 1995 Oct;16(4):557-64
8528172
Stem Cells. 2006 Feb;24(2):386-98
16123384
J Exp Med. 1999 May 3;189(9):1363-72
10224276
J Cell Physiol. 2008 Mar;214(3):588-94
17786951
Transplantation. 2003 Feb 15;75(3):389-97
12589164
Blood. 2003 Nov 15;102(10):3837-44
12881305
Blood. 2004 Jun 15;103(12):4619-21
15001472
Bone Marrow Transplant. 2005 Aug;36(4):355-65
15968279
Cytokine. 2002 Feb 21;17(4):175-81
11991669
Blood. 2005 Mar 1;105(5):2214-9
15514012
J Immunol. 1999 Sep 15;163(6):3239-49
10477593
Scand J Immunol. 2003 Jan;57(1):11-20
12542793