Artikel
Phenotype and function of dendritic cells in patients with familial Mediterranean fever
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Autoren
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Tanja Funk
- Medizinische Universitätsklinik, Innere Medizin II Onkologie, Hämatologie, Klinische Immunologie, Rheumatologie und Pulmologie, Tübingen
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Vanessa Altdörfer
- Medizinische Universitätsklinik, Innere Medizin II Onkologie, Hämatologie, Klinische Immunologie, Rheumatologie und Pulmologie, Tübingen
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Jörg Henes
- Universitätsklinikum Tübingen, Innere Medizin II Onkologie, Hämatologie, Klinische Immunologie, Rheumatologie und Pulmologie, Tübingen
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Frank Grünebach
- Medizinische Universitätsklinik, Innere Medizin II Onkologie, Hämatologie, Klinische Immunologie, Rheumatologie und Pulmologie, Tübingen
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Daniela Dörfel
- Medizinische Universitätsklinik, Innere Medizin II Onkologie, Hämatologie, Klinische Immunologie, Rheumatologie und Pulmologie, Tübingen; Klinische Kooperationseinheit Translationale Immunologie Deutsches Konsortium für Translationale Krebsforschung (DKTK) Deutsches Krebsforschungszentrum (DKFZ) Partnerstandort Tübingen, Innere Medizin, Tübingen
| Veröffentlicht: | 5. Februar 2019 |
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Gliederung
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Background: Dendritic cells (DC) are sentinels of the immune system that bridge innate and adaptive immunity. They control immune reactions by capturing antigen in peripheral tissue, processing and presenting it with concurrent expression of costimulatory molecules and secretion of cytokines. DC detect specific pathogenic structures through pattern recognition receptors, such as the intracellular NOD-like receptors. These form a signaling protein complex upon stimulation, the inflammasome. Familial Mediterranean fever (FMF) is known to be associated with deregulated inflammasome activity. Considering the important role of DC in immunity, the influence of inflammasome activity on differentiation and function of monocyte-derived DC was analyzed in vitro.
Methods: Peripheral blood of FMF patients and healthy controls was comparatively analyzed. DC subpopulation frequency in freshly isolated peripheral blood mononuclear cells was determined by flow cytometry. Plastic adherent monocytes were cultured with GM-CSF and IL-4 for seven days to generate immature DC (iDC) in vitro. LPS was added as maturation stimulus (mDC). iDC and mDC phenotype and function were analyzed by immunostaining, mixed lymphocyte reaction (MLR) and migration assays. To analyze statistical significance Mann-Whitney-U-tests were performed.
Results: No differences in peripheral blood DC subpopulation frequencies between FMF patients and healthy controls could be observed. Immunophenotypic characterization of FMF-iDC revealed a significantly increased expression of the maturation marker CD83, the costimulatory molecule CD86 and HLA-DR. CD209, also known as DC-specific C-type lectin (DC-SIGN) was significantly downregulated. In comparison to healthy controls, FMF-iDC displayed a significantly higher capacity to stimulate the proliferation of allogeneic T cells exceeding even the potential of the mDC from healthy controls. This statistically significant difference in stimulatory potency is sustained in mDC. Moreover, iDC from FMF patients displayed a significantly higher capacity to migrate toward CCL19 as compared to healthy controls.
Conclusion: In summary, in vitro generated FMF-iDC exhibit changes towards a more mature phenotype. Crucial DC functions like T cell stimulation and migration are enhanced in FMF-DC and comparable with more mature cells. Taken together, DC from FMF patients display a transition towards a more mature phenotype and function as typically induced by maturation stimuli such as TLR-L, TNF-α or CD40L.
