The autoimmune condition, Celiac Disease (CeD), displays broad clinical symptoms due to gluten exposure. Its genetic association with DQ variants in the human leukocyte antigen (HLA) system has been recognised. Monocyte-derived mature dendritic cells (MoDCs) present gluten peptides through HLA-DQ and co-stimulatory molecules to T lymphocytes, eliciting a cytokine-rich microenvironment. Having access to CeD associated families prevalent in the Czech Republic, this study utilised an in vitro model to investigate their differential monocyte profile. The higher monocyte yields isolated from PBMCs of CeD patients versus control individuals also reflected the greater proportion of dendritic cells derived from these sources following lipopolysaccharide (LPS)/ peptic-tryptic-gliadin (PTG) fragment stimulation. Cell surface markers of CeD monocytes and MoDCs were subsequently profiled. This foremost study identified a novel bio-profile characterised by elevated CD64 and reduced CD33 levels, unique to CD14++ monocytes of CeD patients. Normalisation to LPS stimulation revealed the increased sensitivity of CeD-MoDCs to PTG, as shown by CD86 and HLA-DQ flow cytometric readouts. Enhanced CD86 and HLA-DQ expression in CeD-MoDCs were revealed by confocal microscopy. Analysis highlighted their dominance at the CeD-MoDC membrane in comparison to controls, reflective of superior antigen presentation ability. In conclusion, this investigative study deciphered the monocytes and MoDCs of CeD patients with the identification of a novel bio-profile marker of potential diagnostic value for clinical interpretation. Herein, the characterisation of CD86 and HLA-DQ as activators to stimulants, along with robust membrane assembly reflective of efficient antigen presentation, offers CeD targeted therapeutic avenues worth further exploration.
- MeSH
- autoimunitní nemoci imunologie MeSH
- biologické markery metabolismus MeSH
- buněčná membrána metabolismus MeSH
- CD antigeny metabolismus MeSH
- celiakie epidemiologie imunologie MeSH
- cytotoxické T-lymfocyty imunologie MeSH
- dendritické buňky imunologie MeSH
- dospělí MeSH
- gliadin škodlivé účinky MeSH
- HLA-DQ antigeny metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- lipopolysacharidy MeSH
- mladiství MeSH
- mladý dospělý MeSH
- monocyty metabolismus MeSH
- náchylnost k nemoci MeSH
- prezentace antigenu imunologie MeSH
- rodina MeSH
- rodokmen MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
To elucidate the role of innate immune responses in celiac disease, we investigated the effect of gliadin on blood monocytes from patients with celiac disease. Gliadin induced substantial TNF-alpha and IL-8 production by monocytes from patients with active celiac disease, lower levels by monocytes from patients with inactive celiac disease, and even lower levels by monocytes from healthy donors. In healthy donor monocytes gliadin induced IL-8 from monocytes expressing HLA-DQ2 and increased monocyte expression of the costimulatory molecules CD80 and CD86, the dendritic cell marker CD83, and the activation marker CD40. Gliadin also increased DNA binding activity of NF-kappaB p50 and p65 subunits in monocytes from celiac patients, and NF-kappaB inhibitors reduced both DNA binding activity and cytokine production. Thus, gliadin activation of HLA-DQ2(+) monocytes leading to chemokine and proinflammatory cytokine production may contribute to the host innate immune response in celiac disease.
- MeSH
- aktivace makrofágů imunologie MeSH
- antigeny CD40 metabolismus MeSH
- antigeny CD80 metabolismus MeSH
- antigeny CD86 metabolismus MeSH
- CD antigeny metabolismus MeSH
- celiakie imunologie metabolismus MeSH
- cytokiny biosyntéza MeSH
- financování organizované MeSH
- gliadin metabolismus MeSH
- HLA-DQ antigeny metabolismus MeSH
- imunoglobuliny metabolismus MeSH
- interleukin-8 biosyntéza MeSH
- lidé MeSH
- membránové glykoproteiny metabolismus MeSH
- monocyty metabolismus MeSH
- NF-kappa B metabolismus MeSH
- peptidové fragmenty MeSH
- průtoková cytometrie MeSH
- TNF-alfa biosyntéza MeSH
- Check Tag
- lidé MeSH