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Autologous tolerogenic dendritic cells derived from monocytes of systemic lupus erythematosus patients and healthy donors show a stable and immunosuppressive phenotype
- Source :
- Immunology. 152:648-659
- Publication Year :
- 2017
- Publisher :
- Wiley, 2017.
-
Abstract
- Systemic lupus erythematosus (SLE) is an autoimmune disease with unrestrained T‐cell and B‐cell activity towards self‐antigens. Evidence shows that apoptotic cells (ApoCells) trigger an autoreactive response against nuclear antigens in susceptible individuals. In this study, we focus on generating and characterizing tolerogenic dendritic cells (tolDCs) to restore tolerance to ApoCells. Monocyte‐derived dendritic cells (DCs) from healthy controls and patients with SLE were treated with dexamethasone and rosiglitazone to induce tolDCs. Autologous apoptotic lymphocytes generated by UV irradiation were given to tolDCs as a source of self‐antigens. Lipopolysaccharide (LPS) was used as a maturation stimulus to induce the expression of co‐stimulatory molecules and secretion of cytokines. TolDCs generated from patients with SLE showed a reduced expression of co‐stimulatory molecules after LPS stimulation compared with mature DCs. The same phenomenon was observed in tolDCs treated with ApoCells and LPS. In addition, ApoCell‐loaded tolDCs stimulated with LPS secreted lower levels of interleukin‐6 (IL‐6) and IL‐12p70 than mature DCs without differences in IL‐10 secretion. The functionality of tolDCs was assessed by their capacity to prime allogeneic T cells. TolDCs displayed suppressor properties as demonstrated by a significantly reduced capacity to induce allogeneic T‐cell proliferation and activation. ApoCell‐loaded tolDCs generated from SLE monocytes have a stable immature/tolerogenic phenotype that can modulate CD4+ T‐cell activation. These properties make them suitable for an antigen‐specific immunotherapy for SLE.
- Subjects :
- Adult
Lipopolysaccharides
Male
0301 basic medicine
Lipopolysaccharide
Ultraviolet Rays
medicine.medical_treatment
Immunology
Stimulation
medicine.disease_cause
Monocytes
Autoimmunity
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Antigen
medicine
Humans
Lupus Erythematosus, Systemic
Immunology and Allergy
Secretion
Lymphocytes
Autografts
Aged
Immunosuppression Therapy
Autoimmune disease
Interleukin-6
business.industry
Original Articles
Dendritic Cells
Immunotherapy
Middle Aged
medicine.disease
Interleukin-12
Tissue Donors
Interleukin-10
030104 developmental biology
chemistry
Apoptosis
Female
business
030215 immunology
Subjects
Details
- ISSN :
- 00192805
- Volume :
- 152
- Database :
- OpenAIRE
- Journal :
- Immunology
- Accession number :
- edsair.doi.dedup.....3701e31d4973030725941136578611a6