Secretomes Derived from Osteogenically Differentiated Jaw Periosteal Cells Inhibit Phenotypic and Functional Maturation of CD14 Monocyte-derived Dendritic Cells

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2023 Jan 26

PMID 36700194

Authors

Wanjing Cen

Felix Umrath

Antonio Jose Salgado

Siegmar Reinert

Dorothea Alexander

Affiliations

Soon will be listed here.

Abstract

The jaw periosteal tissue is generally recognized as a suitable source for the isolation of mesenchymal stem cells (MSCs). In previous studies we showed evidence that two- and three-dimensionally cultured jaw periosteum-derived MSCs (JPCs) are able to induce a more immature phenotype of dendritic cells (DCs). To further expand our knowledge of JPCs' immunoregulative function, we investigated the effects of JPC secretomes derived from undifferentiated (CO) or osteogenically differentiated cells (treated with or without dexamethasone: OB+/-D) on CD14 monocyte-derived DCs (MoDCs). We detected a remarkably reduced formation of MoDC homotypic clusters under the influence of secretomes from osteogenically induced JPCs. Further, significantly decreased numbers of CD83 cells, up-regulated CD209 and down-regulated CD80, CD86 and CD197 expression levels were detected on the surface of MoDCs. Whereas secretomes from JPCs osteogenically stimulated with dexamethasone significantly enhanced FITC-dextran uptake capacity of MoDCs, the increase by secretomes of JPCs treated without dexamethasone did not reach significance. The analysis of mixed lymphocyte reactions revealed that OB+/-D secretomes were able to significantly reduce the numbers of proliferating CD14 peripheral blood mononuclear cells (PBMCs) and of proliferating CD4 T cells. The OB-D secretome significantly promoted the expansion of regulatory CD25 T cells. Regarding gene expression of MoDCs, remarkably up-regulated mRNA expression of CD209, HLA-DRA, CSF3, IL10 and IL8 was detected when DCs were cultured in the presence of OB+/-D secretomes. At the same time, secretomes seemed to have an impact in the down-regulation of IFNγ and IL12B gene expression. At protein level, OB+/-D secretomes significantly up-regulated IL-10 and IDO (indoleamine-pyrrole 2,3-dioxygenase) levels whereas IL-12/IL-23p40 levels were down-regulated in supernatants of MoDCs when cultured under the presence of OB+/-D secretomes. Taken together, while secretomes from untreated JPCs had only little effects on the process of maturation of MoDCs, secretomes derived from osteogenically induced JPCs were able to inhibit the phenotypic and functional maturation of MoDCs.

References

Geijtenbeek T, Torensma R, van Vliet S, van Duijnhoven G, Adema G, van Kooyk Y . Identification of DC-SIGN, a novel dendritic cell-specific ICAM-3 receptor that supports primary immune responses. Cell. 2000; 100(5):575-85. DOI: 10.1016/s0092-8674(00)80693-5. View

Azuma M, Ito D, Yagita H, Okumura K, Phillips J, Lanier L . B70 antigen is a second ligand for CTLA-4 and CD28. Nature. 1993; 366(6450):76-9. DOI: 10.1038/366076a0. View

Couper K, Blount D, Riley E . IL-10: the master regulator of immunity to infection. J Immunol. 2008; 180(9):5771-7. DOI: 10.4049/jimmunol.180.9.5771. View

Wanner Y, Umrath F, Waidmann M, Reinert S, Alexander D . Platelet Lysate: The Better Choice for Jaw Periosteal Cell Mineralization. Stem Cells Int. 2018; 2017:8303959. PMC: 5748149. DOI: 10.1155/2017/8303959. View

Termeer C, Johannsen H, Braun T, Renkl A, Ahrens T, Denfeld R . The role of CD44 during CD40 ligand-induced dendritic cell clustering and maturation. J Leukoc Biol. 2001; 70(5):715-22. View

Stobie L, Gurunathan S, Prussin C, Sacks D, Glaichenhaus N, Wu C . The role of antigen and IL-12 in sustaining Th1 memory cells in vivo: IL-12 is required to maintain memory/effector Th1 cells sufficient to mediate protection to an infectious parasite challenge. Proc Natl Acad Sci U S A. 2000; 97(15):8427-32. PMC: 26964. DOI: 10.1073/pnas.160197797. View

Steinman R, Hawiger D, Liu K, Bonifaz L, Bonnyay D, Mahnke K . Dendritic cell function in vivo during the steady state: a role in peripheral tolerance. Ann N Y Acad Sci. 2003; 987:15-25. DOI: 10.1111/j.1749-6632.2003.tb06029.x. View

Azuma M, Cayabyab M, Buck D, Phillips J, Lanier L . CD28 interaction with B7 costimulates primary allogeneic proliferative responses and cytotoxicity mediated by small, resting T lymphocytes. J Exp Med. 1992; 175(2):353-60. PMC: 2119127. DOI: 10.1084/jem.175.2.353. View

Beyth S, Borovsky Z, Mevorach D, Liebergall M, Gazit Z, Aslan H . Human mesenchymal stem cells alter antigen-presenting cell maturation and induce T-cell unresponsiveness. Blood. 2004; 105(5):2214-9. DOI: 10.1182/blood-2004-07-2921. View

10.

Pierre P, Turley S, Gatti E, Hull M, Meltzer J, Mirza A . Developmental regulation of MHC class II transport in mouse dendritic cells. Nature. 1997; 388(6644):787-92. DOI: 10.1038/42039. View

11.

Cooper A, Khader S . IL-12p40: an inherently agonistic cytokine. Trends Immunol. 2006; 28(1):33-8. DOI: 10.1016/j.it.2006.11.002. View

12.

Watowich S, Liu Y . Mechanisms regulating dendritic cell specification and development. Immunol Rev. 2010; 238(1):76-92. PMC: 3039024. DOI: 10.1111/j.1600-065X.2010.00949.x. View

13.

Lehner M, Stockl J, Majdic O, Knapp W, Huttner K, Felzmann T . MHC class II antigen signaling induces homotypic and heterotypic cluster formation of human mature monocyte derived dendritic cells in the absence of cell death. Hum Immunol. 2003; 64(8):762-70. DOI: 10.1016/s0198-8859(03)00094-6. View

14.

Steinman R, Nussenzweig M . Avoiding horror autotoxicus: the importance of dendritic cells in peripheral T cell tolerance. Proc Natl Acad Sci U S A. 2002; 99(1):351-8. PMC: 117564. DOI: 10.1073/pnas.231606698. View

15.

Vasaturo A, Di Blasio S, Peeters D, de Koning C, de Vries J, Figdor C . Clinical Implications of Co-Inhibitory Molecule Expression in the Tumor Microenvironment for DC Vaccination: A Game of Stop and Go. Front Immunol. 2013; 4:417. PMC: 3847559. DOI: 10.3389/fimmu.2013.00417. View

16.

Li Z, Ju X, Silveira P, Abadir E, Hsu W, Hart D . CD83: Activation Marker for Antigen Presenting Cells and Its Therapeutic Potential. Front Immunol. 2019; 10:1312. PMC: 6568190. DOI: 10.3389/fimmu.2019.01312. View

17.

Zhang W, Ge W, Li C, You S, Liao L, Han Q . Effects of mesenchymal stem cells on differentiation, maturation, and function of human monocyte-derived dendritic cells. Stem Cells Dev. 2004; 13(3):263-71. DOI: 10.1089/154732804323099190. View

18.

Steinman R, Hawiger D, Nussenzweig M . Tolerogenic dendritic cells. Annu Rev Immunol. 2003; 21:685-711. DOI: 10.1146/annurev.immunol.21.120601.141040. View

19.

Matta B, Castellaneta A, Thomson A . Tolerogenic plasmacytoid DC. Eur J Immunol. 2010; 40(10):2667-76. PMC: 3974856. DOI: 10.1002/eji.201040839. View

20.

He F, Umrath F, Reinert S, Alexander D . Jaw Periosteum-Derived Mesenchymal Stem Cells Regulate THP-1-Derived Macrophage Polarization. Int J Mol Sci. 2021; 22(9). PMC: 8122347. DOI: 10.3390/ijms22094310. View