BACKGROUND AND AIMS: CD68+ cells are a potent source of inflammatory cytokines in adipose tissue and myocardium. The development of low-grade inflammation in adipose tissue is implicated in the pathogenesis of obesity-associated disorders including type 2 diabetes mellitus (T2DM) and cardiovascular disease. The main aim of the study was to characterize and quantify myocardial and adipose tissue CD68+ cells and adipose tissue crown-like structures (CLS) in patients with obesity, coronary artery disease (CAD) and T2DM. METHODS AND RESULTS: Samples were obtained from the right atrium, epicardial (EAT) and subcutaneous adipose tissue (SAT) during elective heart surgery (non-obese, n = 34 patients; obese, n = 24 patients). Immunohistochemistry was used to visualize CD68+ cells. M1-polarized macrophages were visualized by immunohistochemical detection of CD11c. The proportion of CD68+ cells was higher in EAT than in SAT (43.4 ± 25.0 versus 32.5 ± 23.1 cells per 1 mm2; p = 0.015). Myocardial CD68+ cells were more abundant in obese patients (45.6 ± 24.5 versus 27.7 ± 14.8 cells per 1 mm2; p = 0.045). In SAT, CD68+ cells were more frequent in CAD patients (37.3 ± 23.0 versus 23.1 ± 20.9 cells per 1 mm2; p = 0.012). Patients having CLS in their SAT had higher average BMI (34.1 ± 6.4 versus 29.0 ± 4.5; p = 0.024). CONCLUSIONS: Regional-based increases in the frequency of CD68+ cells and changes of their phenotype in CLS were detected in obese patients and CAD patients. Therapeutic modulation of adipose tissue inflammation may represent a target for treatment of obesity.

• MeSH
• antigeny CD11c analýza   MeSH
• antigeny diferenciační myelomonocytární analýza   MeSH
• biologické markery analýza   MeSH
• CD antigeny analýza   MeSH
• diabetes mellitus 2. typu imunologie   patologie   MeSH
• dospělí MeSH
• fenotyp MeSH
• lidé středního věku MeSH
• lidé MeSH
• makrofágy imunologie   patologie   MeSH
• myokard imunologie   patologie   MeSH
• nemoci koronárních tepen imunologie   patologie   MeSH
• obezita imunologie   patologie   MeSH
• počet buněk MeSH
• podkožní tuk imunologie   patologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• zánět imunologie   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

The intestinal immune system can respond to invading pathogens yet maintain immune tolerance to self-antigens and microbiota. Myeloid cells are central to these processes, but the signaling pathways that underlie tolerance versus inflammation are unclear. Here we show that mice lacking Calcineurin B in CD11chighMHCII+ cells (Cnb1 CD11c mice) spontaneously develop intestinal inflammation and are susceptible to induced colitis. In these mice, colitis is associated with expansion of T helper type 1 (Th1) and Th17 cell populations and a decrease in the number of FoxP3+ regulatory T (Treg) cells, and the pathology is linked to the inability of intestinal Cnb1-deficient CD11chighMHCII+ cells to express IL-2. Deleting IL-2 in CD11chighMHCII+ cells induces spontaneous colitis resembling human inflammatory bowel disease. Our findings identify that the calcineurin-NFAT-IL-2 pathway in myeloid cells is a critical regulator of intestinal homeostasis by influencing the balance of inflammatory and regulatory responses in the mouse intestine.

• MeSH
• antigeny CD11c genetika   imunologie   MeSH
• buňky Th17 imunologie   MeSH
• geny MHC třídy II MeSH
• homeostáza MeSH
• interleukin-2 genetika   imunologie   MeSH
• kalcineurin genetika   imunologie   MeSH
• kolitida genetika   imunologie   MeSH
• lidé MeSH
• myeloidní buňky imunologie   MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• myši MeSH
• střeva imunologie   MeSH
• Th1 buňky imunologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Treatment of post-transplant patients with immunosuppressive drugs targeting the calcineurin-nuclear factor of activated T cells (NFAT) pathway, including cyclosporine A or tacrolimus, is commonly associated with a higher incidence of opportunistic infections, such as Aspergillus fumigatus, which can lead to severe life-threatening conditions. A component of the A. fumigatus cell wall, β-glucan, is recognized by dendritic cells (DCs) via the Dectin-1 receptor, triggering downstream signaling that leads to calcineurin-NFAT binding, NFAT translocation, and transcription of NFAT-regulated genes. Here, we address the question of whether calcineurin signaling in CD11c-expressing cells, such as DCs, has a specific role in the innate control of A. fumigatus. Impairment of calcineurin in CD11c-expressing cells (CD11ccrecnb1loxP) significantly increased susceptibility to systemic A. fumigatus infection and to intranasal infection in irradiated mice undergoing bone marrow transplant. Global expression profiling of bone marrow-derived DCs identified calcineurin-regulated processes in the immune response to infection, including expression of pentraxin-3, an important antifungal defense protein. These results suggest that calcineurin inhibition directly impairs important immunoprotective functions of myeloid cells, as shown by the higher susceptibility of CD11ccrecnbloxP mice in models of systemic and invasive pulmonary aspergillosis, including after allogeneic bone marrow transplantation. These findings are relevant to the clinical management of transplant patients with severe Aspergillus infections.

• MeSH
• antigeny CD11c metabolismus   MeSH
• Aspergillus fumigatus imunologie   MeSH
• aspergilóza imunologie   MeSH
• C-reaktivní protein genetika   metabolismus   MeSH
• dendritické buňky imunologie   MeSH
• down regulace MeSH
• imunosupresiva škodlivé účinky   terapeutické užití   MeSH
• inhibitory kalcineurinu škodlivé účinky   terapeutické užití   MeSH
• kalcineurin genetika   metabolismus   MeSH
• kultivované buňky MeSH
• lidé MeSH
• myši inbrední BALB C MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• myši MeSH
• náchylnost k nemoci MeSH
• rejekce štěpu prevence a kontrola   MeSH
• sérový amyloidový protein genetika   metabolismus   MeSH
• signální transdukce MeSH
• transplantace kostní dřeně * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Pig is a domestic species of major importance in the agro-economy and in biomedical research. Mononuclear phagocytes (MNP) are organized in subsets with specialized roles in the orchestration of the immune response and new tools are awaited to improve MNP subset identification in the pig. We cloned pig CD11c cDNA and generated a monoclonal antibody to pig CD11c which showed a pattern of expression by blood and skin MNP subsets similar to humans. We also developed a porcine XCL1-mCherry dimer which specifically reacted with the XCR1-expressing dendritic cell subset of the type 1 lineage in blood and skin. These original reagents will allow the efficient identification of pig MNP subsets to study their role in physiological and pathological processes and also to target these cells in novel intervention and vaccine strategies for veterinary applications and preclinical evaluations.

• MeSH
• antigeny CD11c imunologie   metabolismus   MeSH
• dendritické buňky fyziologie   MeSH
• fagocyty imunologie   MeSH
• imunologické testy metody   MeSH
• klonování DNA MeSH
• kůže metabolismus   MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• monoklonální protilátky metabolismus   MeSH
• mononukleární fagocytární systém * MeSH
• prasata imunologie   MeSH
• receptory spřažené s G-proteiny imunologie   metabolismus   MeSH
• veterinární lékařství MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

1. Patients with arthritis will be examined in the Early Arthritis Clinic based on referral by a primary care physician within 2 weeks. The cohort will be prospectively followed, clinical exams, laboratory tests and imaging studies will be performed in accordance with a prespecified schedule. Results will be recorded in electronic CRF. 2. Total RNA will be isolated from whole blood, mRNA will be transcribed to cDNA and expression profile of 90 genes targeted for their possible important role in immune inflammatory response will be performed using the TaqMan Low Density Array. 3. CD11c on monocytes will be measured after separation of the population of inflammatory a resident monocytes (CD14+/CD16dim a CD14+/CD16bright) in samples obtained at baseline and follow-up visits. 4. Levels of selected S100 proteins will be measured in serum and/or plasma using commercial ELISA kits (CircuLex). Measurements will be done at baseline, at 3 months and possibly after a year.

1. V ambulanci pro časnou artritidu budou vyšetřeni nemocní s klinicky přítomnou artritidou na doporučení ošetřujícího lékaře do 2 týdnů. Kohorta bude prospektivně sledována, podle předem určeného harmonogramu budou prováděna klinická, laboratorní a zobrazovací vyšetření. Výsledky budou zaznamenávány do elektronického CRF. 2. Celková RNA bude izolována z plné periferní krve, mRNA bude převedena na cDNA a pomocí TaqMan Low Density Array bude detekován expresní profil 90 genů vytypovaných pro možnou významnou úlohu v imunitní zánětlivé reakci. 3. CD11c na monocytech bude měřeno po vymezení populace zánětlivých a rezidentních monocytů (CD14+/CD16dim a CD14+/CD16bright) ve vzorcích získaných na počátku onemocnění a při každé z kontrolních návštěv. 4. Hladiny vybraných S100 proteinů budou stanoveny v séru a/nebo v plazmě pomocí komerčně dostupných ELISA kitů (CircuLex). Měření bude provedeno při zařazení, po 3 měsících a případně po roce.

• MeSH
• ambulantní zařízení MeSH
• antigeny CD11c MeSH
• biologické markery MeSH
• cytokiny MeSH
• ELISA MeSH
• prognóza MeSH
• proteiny S100 analýza   MeSH
• raná péče MeSH
• revmatoidní artritida diagnóza   terapie   MeSH
• rizikové faktory MeSH
• sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů MeSH

• Konspekt
• Biochemie. Molekulární biologie. Biofyzika
• NLK Obory
• revmatologie
• alergologie a imunologie
• biologie
• NLK Publikační typ
• závěrečné zprávy o řešení grantu IGA MZ ČR

The choice of tools that enable efficient targeting of exogenous antigens (Ag) for processing and presentation by professional Ag-presenting cells (APC) remains limited. This represents, indeed, a bottleneck in development of vaccines inducing specific T-cell responses. Here, we describe a novel strategy of Ag delivery into APCs. The Ag of choice is fused to the N- or C-terminus of streptavidin (SA) and tetrameric Ag-SA or SA-Ag fusion proteins are produced in E. coli and purified by 2-Iminobiotin-Agarose affinity chromatography. Alternatively, Ag-SA proteins are purified from urea extracts of E. coli inclusion bodies and refolded in vitro into functional tetramers. Complexes with biotinylated antibodies targeting cell surface receptors are formed and used to deliver the Ags of choice for processing and presentation by APCs and induction of Ag-specific CD4+ and CD8+ T-cell responses in vitro and in vivo.

• MeSH
• antigeny CD11c imunologie   metabolismus   MeSH
• antigeny chemie   genetika   imunologie   metabolismus   MeSH
• biotinylace MeSH
• buněčné linie MeSH
• dendritické buňky imunologie   metabolismus   MeSH
• kur domácí MeSH
• molekulární sekvence - údaje MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• ovalbumin chemie   genetika   imunologie   metabolismus   MeSH
• receptory buněčného povrchu imunologie   metabolismus   MeSH
• rekombinantní fúzní proteiny chemie   genetika   imunologie   metabolismus   MeSH
• rozpustnost MeSH
• sekvence aminokyselin MeSH
• sekvence nukleotidů MeSH
• streptavidin chemie   genetika   imunologie   metabolismus   MeSH
• T-lymfocyty imunologie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Human dendritic cells have distinct roles in the regulation of immunity. In this study we analysed the kinetics and the proportion of myeloid and plasmacytoid subsets of dendritic cells (DC) in peripheral blood of 15 patients with multiple myeloma (MM) before and during treatment that included autologous transplantation. Control group of 15 healthy volunteers was evaluated by using the same approaches. Flowcytometric determination of relative and absolute cell counts in unmanipulated peripheral blood was based on the expression of surface antigens CD83 and HLA-DR. Depending on the expression of CD11c or CD123, we divided these cells into CD11c+ dendritic cells type 1 (DC1) and CD123+ DC type 2 (DC2). Significant differences were found in initial relative counts of CD83+ cells and of the DC2 subtype between the group of controls and the group of patients before treatment. In absolute counts, there was a difference only in the DC2 subtype. After induction treatment (vincristine, doxorubicin, and dexamethasone), the mean percentage of CD83+ DC and the DC1 percentage were significantly higher than initially, but there was no significant difference in absolute counts. Administration of G-CSF again increased the total DC numbers. Intermediate DC counts were found in the apheresis products. After engraftment, we found the highest relative DC numbers, but absolute counts were not very high because of leukopenia. Within six months after transplantation, normal relative and absolute DC counts were found in patients. Untreated patients with MM have significantly lower relative numbers of peripheral blood DC in comparison with healthy volunteers. The highest number of total DC was found after engraftment. The DC1/DC2 ratio showed relative predominance of DC1 subtype and the lowest DC1/DC2 ratio was found in the apheresis products. DC counts comparable with those of healthy volunteers were found in patients six months after transplantation.

• MeSH
• antigeny CD11c metabolismus   MeSH
• autologní transplantace MeSH
• časové faktory MeSH
• CD antigeny metabolismus   MeSH
• dendritické buňky cytologie   klasifikace   MeSH
• dexamethason aplikace a dávkování   MeSH
• doxorubicin aplikace a dávkování   MeSH
• faktor stimulující kolonie granulocytů aplikace a dávkování   MeSH
• financování organizované MeSH
• HLA-DR antigeny metabolismus   MeSH
• imunoglobuliny metabolismus   MeSH
• indukce remise MeSH
• kombinovaná terapie MeSH
• lidé středního věku MeSH
• lidé MeSH
• membránové glykoproteiny metabolismus   MeSH
• mnohočetný myelom imunologie   metabolismus   terapie   MeSH
• počet buněk MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• průtoková cytometrie MeSH
• receptor interleukinu-3 - alfa-podjednotka metabolismus   MeSH
• transplantace periferních kmenových buněk MeSH
• vinkristin aplikace a dávkování   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH

• MeSH
• antigeny CD11c MeSH
• inhibiční faktory migrace leukocytů MeSH
• populace MeSH
• Geografické názvy
• Československo MeSH