Neutrophil and Granulocytic Myeloid-Derived Suppressor Cell-Mediated T Cell Suppression Significantly Contributes to Immune Dysregulation in Common Variable Immunodeficiency Disorders
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
30487174
DOI
10.4049/jimmunol.1800102
PII: jimmunol.1800102
Knihovny.cz E-zdroje
- MeSH
- aktivace neutrofilů MeSH
- antigeny CD11b metabolismus MeSH
- antigeny CD274 metabolismus MeSH
- běžná variabilní imunodeficience imunologie MeSH
- dospělí MeSH
- granulocyty fyziologie MeSH
- imunologická tolerance MeSH
- kultivované buňky MeSH
- lidé středního věku MeSH
- lidé MeSH
- lipokalin-2 krev MeSH
- mladý dospělý MeSH
- myeloidní supresorové buňky fyziologie MeSH
- neutrofily fyziologie MeSH
- reaktivní formy kyslíku metabolismus MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- T-lymfocyty imunologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antigeny CD11b MeSH
- antigeny CD274 MeSH
- CD274 protein, human MeSH Prohlížeč
- LCN2 protein, human MeSH Prohlížeč
- lipokalin-2 MeSH
- reaktivní formy kyslíku MeSH
Common variable immunodeficiency disorders (CVID) represent a group of primary immunodeficiency diseases characterized by hypogammaglobulinemia and impaired specific Ab response, resulting in recurrent infections due to dysfunctional immune response. The specific mechanisms mediating immune deficiency in CVID remain to be determined. Previous studies indicated that immune dysregulation in CVID patients is associated with chronic microbial translocation, systemic immune activation, and altered homeostasis of lymphocytic and myeloid lineages. A detailed phenotypic, functional characterization of plasma markers and immune cell populations was performed in 46 CVID patients and 44 healthy donors. CVID patients displayed significantly elevated plasma levels of a marker of neutrophil activation neutrophil gelatinase-associated lipocalin. Neutrophils from CVID patients exhibited elevated surface levels of CD11b and PD-L1 and decreased levels of CD62L, CD16, and CD80, consistent with a phenotype of activated neutrophils with suppressive properties. Neutrophils from CVID patients actively suppressed T cell activation and release of IFN-γ via the production of reactive oxygen species. Furthermore, CVID was associated with an increased frequency of low-density neutrophils (LDNs)/granulocytic myeloid-derived suppressor cells. LDN/granulocytic myeloid-derived suppressor cell frequency in CVID patients correlated with reduced T cell responsiveness. Exogenous stimulation of whole blood with bacterial LPS emulated some but not all of the phenotypic changes observed on neutrophils from CVID patients and induced neutrophil population with LDN phenotype. The presented data demonstrate that neutrophils in the blood of CVID patients acquire an activated phenotype and exert potent T cell suppressive activity. Specific targeting of myeloid cell-derived suppressor activity represents a novel potential therapeutic strategy for CVID.
Central European Institute of Technology Masaryk University 601 77 Brno Czech Republic; and
Centre for Cardiovascular Surgery and Transplantation 656 91 Brno Czech Republic
Department of Microbiology University of Alabama at Birmingham Birmingham AL 35294
Department of Pathology University of Alabama at Birmingham Birmingham AL 35249
Citace poskytuje Crossref.org
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