Mesenchymal stem cells derived from human exfoliated deciduous teeth (SHEDs) induce immune modulatory profile in monocyte-derived dendritic cells.
BACKGROUND
Mesenchymal stem cells have prominent immune modulatory properties, which may have clinical applications; however their major source, bone marrow, is of limited availability. On the other hand, mesenchymal stem cells derived from human exfoliated deciduous teeth (SHEDs) are readily accessible, but their immune regulatory properties have not been completely investigated. This study was designed, therefore, to evaluate the SHEDs influence on DCs differentiation, maturation, ability to activate T cells and to expand CD4(+)Foxp3(+) T cells.


RESULTS
The experiments were based in cellular co-culture during differentiation and maturation of monocyte derived-DCs (moDCs), with, or not, presence of SHEDs. After co-culture with SHEDs, (moDCs) presented lower expression of BDCA-1 and CD11c, in comparison to DC cultivated without SHEDs. CD40, CD80, CD83 and CD86 levels were also decreased in mature DCs (mDCs) after co-cultivation with SHEDs. To assess the ability of SHEDs-exposed moDCs to modulate T cell responses, the former were separated from SHEDs, and co-cultured with peripheral blood lymphocytes. After 5 days, the proliferation of CD4(+) and CD8(+) T cells was evaluated and found to be lower than that induced by moDCs cultivated without SHEDs. In addition, an increase in the proportion of CD4(+)Foxp3(+)IL-10(+) T cells was observed among cells stimulated by mature moDCs that were previously cultivated with SHEDs. Soluble factors released during co-cultures also showed a reduction in the pro-inflammatory cytokines (IL-2, TNF-α and IFN-γ), and an increase in the anti-inflammatory molecule IL-10.


CONCLUSIONS
This study shows that SHEDs induce an immune regulatory phenotype in moDCs cells, evidenced by changes in maturation and differentiation rates, inhibition of lymphocyte stimulation and ability to expand CD4(+)Foxp3(+) T cells. Further characterization and validation of this phenomenon could support the use of SHEDs, directly or indirectly for immune modulation in the clinical practice.
Biomedical Science Institute, University of São Paulo, São Paulo, Brazil; Dentistry Department, University of São Paulo, São Paulo, Brazil; Biomedical Science Institute, University of Juiz de Fora, Juiz de Fora, Brazil.
Fernando de Sá
Fde S
Silva
Biomedical Science Institute, University of São Paulo, São Paulo, Brazil.
Rodrigo Nalio
RN
Ramos
Biomedical Science Institute, University of São Paulo, São Paulo, Brazil.
Danilo Candido
DC
de Almeida
Biomedical Science Institute, University of São Paulo, São Paulo, Brazil.
Enio Jose
EJ
Bassi
Biomedical Science Institute, University of São Paulo, São Paulo, Brazil.
Roberto Pereira
RP
Gonzales
Dentistry Department, University of São Paulo, São Paulo, Brazil.
Sueli Patricia Harumi
SP
Miyagi
Biomedical Science Institute, University of Juiz de Fora, Juiz de Fora, Brazil.
Claudinéia Pereira
CP
Maranduba
Biomedical Science Institute, University of Juiz de Fora, Juiz de Fora, Brazil.
Osvaldo Augusto Brazil Esteves
OA
Sant'Anna
Immunochemistry Laboratory, Butantan Institute, São Paulo, Brazil.
Márcia Martins
MM
Marques
Biomedical Science Institute, University of São Paulo, São Paulo, Brazil.
José Alexandre Marzagão
JA
Barbuto
Biomedical Science Institute, University of São Paulo, São Paulo, Brazil.
Niels Olsen Saraiva
NO
Câmara
Biomedical Science Institute, University of Juiz de Fora, Juiz de Fora, Brazil.
Carlos Magno
CM
da Costa Maranduba
D018949:Antigens, CD1 / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D002454:Cell Differentiation; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D056747:Immunomodulation; D016753:Interleukin-10 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D014080:Tooth Exfoliation / Q000276:immunology* / Q000378:metabolism*
D018949:Antigens, CD1; D015415:Biomarkers; C437944:CD1C protein, human; D019013:CD40 Antigens; D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D006023:Glycoproteins; D016753:Interleukin-10