PURPOSE: Esophageal cancer (EC) is one of the most lethal gastrointestinal malignancies. Immunotherapy is a promising treatment modality for this disease. However, broader implementation of EC immunotherapy has been discouraged because of insufficient understanding of tumor interactions with the immune system. As with other malignancies, the current research on EC focuses on deciphering the immune cell signatures within the tumor microenvironment. However, the disease-elicited immune cell profiles in the paratumoral compartments are largely unknown. METHODS: We examined the immune cell signatures in 62 tissue samples from 16 EC patients in different esophageal tissue compartments: tumor tissue, peritumoral tissue, healthy esophageal tissue, and adjacent lymph nodes. We analyzed the proportions and distribution patterns of NK cells and CD4+ and CD8+ T cells as well as their death receptor (FasR, FasR/DR3)-expressing subpopulations. The analyzed data were then compared and correlated with the patients' clinicopathological data. RESULTS: We found that the FasR+ NK cells, CD4+ and CD8+ T cells infiltrated lymph nodes at the lowest levels and that the FasR+DR3+ CD4+ T cells were enhanced in tumors. The comparisons with the clinicopathological data revealed a major impact of active smoking on the reduction in paratumoral NK cells and the upregulation of FasR in tumor-infiltrating NK and CD8+ T cells. The lymph node metastatic stage, tumor stage, and Mandard grade correlated with the compartmental proportions of the evaluated immune cells. CONCLUSION: The novel association of the disease state with tumoral and paratumoral immune cell signatures suggests new possibilities for personalized immunotherapy for EC patients.

• MeSH
• adenokarcinom imunologie   patologie   terapie   MeSH
• antigeny CD95 imunologie   MeSH
• buňky NK imunologie   patologie   MeSH
• CD4-pozitivní T-lymfocyty imunologie   patologie   MeSH
• CD8-pozitivní T-lymfocyty imunologie   patologie   MeSH
• imunoterapie metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfatické uzliny imunologie   patologie   MeSH
• lymfocyty imunologie   patologie   MeSH
• nádory jícnu imunologie   patologie   terapie   MeSH
• senioři MeSH
• skvamózní karcinom jícnu imunologie   patologie   terapie   MeSH
• studie případů a kontrol MeSH
• T-lymfocyty - podskupiny imunologie   patologie   MeSH
• tumor infiltrující lymfocyty imunologie   patologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Regulatory T (Treg) cells prevent autoimmunity by limiting immune responses and inflammation in the secondary lymphoid organs and nonlymphoid tissues. While unique subsets of Treg cells have been described in some nonlymphoid tissues, their relationship to Treg cells in secondary lymphoid organs and circulation remains unclear. Furthermore, it is possible that Treg cells from similar tissue types share largely similar properties. We have identified a short-lived effector Treg cell subset that expresses the α2 integrin, CD49b, and exhibits a unique tissue distribution, being abundant in peripheral blood, vasculature, skin, and skin-draining lymph nodes, but uncommon in the intestines and in viscera-draining lymph nodes. CD49b+ Treg cells, which display superior functionality revealed by in vitro and in vivo assays, appear to develop after multiple rounds of cell division and TCR-dependent activation. Accordingly, single-cell RNA-seq analysis placed these cells at the apex of the Treg developmental trajectory. These results shed light on the identity and development of a functionally potent subset of mature effector Treg cells that recirculate through and survey peripheral tissues.

• MeSH
• cévy imunologie   MeSH
• imunitní dozor * MeSH
• integrin alfa2 genetika   imunologie   MeSH
• kůže krevní zásobení   cytologie   imunologie   MeSH
• lymfatické uzliny krevní zásobení   cytologie   imunologie   MeSH
• myši transgenní MeSH
• myši MeSH
• regulační T-lymfocyty cytologie   imunologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

While autoimmune T cells are present in most individuals, only a minority of the population suffers from an autoimmune disease. To better appreciate the limits of T cell tolerance, we carried out experiments to determine how many autoimmune T cells are required to initiate an experimental autoimmune disease. Variable numbers of autoimmune OT-I T cells were transferred into RIP-OVA mice, which were injected with antigen-loaded DCs in a single footpad; this restricted T cell priming to a few OT-I T cells that are present in the draining popliteal lymph node. Using selective plane illumination microscopy (SPIM) we counted the number of OT-I T cells present in the popliteal lymph node at the time of priming. Analysis of our data suggests that a single autoimmune T cell cannot induce an experimental autoimmune disease, but a "quorum" of 2-5 autoimmune T cells clearly has this capacity.

• MeSH
• autoimunita * MeSH
• autoimunitní nemoci imunologie   MeSH
• CD8-pozitivní T-lymfocyty cytologie   imunologie   MeSH
• dendritické buňky imunologie   MeSH
• experimentální diabetes mellitus imunologie   MeSH
• imunologická tolerance MeSH
• lymfatické uzliny cytologie   imunologie   MeSH
• modely nemocí na zvířatech MeSH
• myši transgenní MeSH
• myši MeSH
• ovalbumin imunologie   MeSH
• převzatá imunita MeSH
• prezentace antigenu MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• erytrocyty fyziologie   imunologie   MeSH
• imunitní systém * cytologie   růst a vývoj   MeSH
• krevní buňky klasifikace   MeSH
• lidé MeSH
• lymfatické uzliny fyziologie   imunologie   krevní zásobení   MeSH
• lymfatický systém fyziologie   imunologie   MeSH
• makrofágy fyziologie   klasifikace   MeSH
• mononukleární fagocytární systém imunologie   MeSH
• slezina imunologie   MeSH
• trombocyty fyziologie   imunologie   MeSH
• zánět imunologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Rheumatoid arthritis (RA) is a chronic autoimmune disease with significant morbidity and mortality. Recent studies suggest that modulation of adenosine signaling, a potent immunosuppressive pathway, is a promising approach for treatment of RA. Extracellular adenosine can come from two sources: transport of intracellular adenosine and hydrolysis of extracellular adenine nucleotides by CD73. In this study, we investigated the susceptibility of CD73-deficient C57BL/6 mice to collagen-induced arthritis (CIA), a well-established mouse model of RA. Our data demonstrated that CD73-deficient mice are significantly more susceptible to CIA than wild-type mice. CD73 deficiency resulted in an increased production of proinflammatory cytokines in the joints, increased Th1 T cell responses, and increased joint destruction. Surprisingly, this was accompanied by delayed anticollagen IgG responses, suggesting defective isotype class switching in CD73-deficient mice. Using bone marrow chimera mice, we demonstrated that CD73 expression on nonhematopoietic cells, but not on hematopoietic cells, was important for protection from CIA. We further demonstrated that administration of a selective A2A adenosine receptor agonist to CD73-deficient mice resulted in arthritis incidence similar to wild-type mice in support of a protective role for A2A signaling. Taken together, our study identifies CD73 as an important regulator of CIA in mice. It also strengthens the notion that CD73-generated adenosine by nonhematopoietic cells plays a protective role in RA and suggests that strategies able to enhance CD73 activity or expression levels may be a valid therapeutic option.

• MeSH
• 5'-nukleotidasa nedostatek   genetika   imunologie   MeSH
• adenosin analogy a deriváty   farmakologie   MeSH
• agonisté adenosinového receptoru A2 farmakologie   MeSH
• artritida experimentální genetika   imunologie   prevence a kontrola   MeSH
• CD4-pozitivní T-lymfocyty imunologie   metabolismus   MeSH
• cytokiny imunologie   metabolismus   MeSH
• ELISA MeSH
• fenethylaminy farmakologie   MeSH
• imunoglobulin G imunologie   MeSH
• interferon gama imunologie   metabolismus   MeSH
• klouby imunologie   metabolismus   patologie   MeSH
• kolagen typ II imunologie   MeSH
• kur domácí MeSH
• lymfatické uzliny imunologie   metabolismus   MeSH
• mediátory zánětu imunologie   metabolismus   MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• náchylnost k nemoci imunologie   MeSH
• odolnost vůči nemocem genetika   imunologie   MeSH
• ptačí proteiny imunologie   MeSH
• Th1 buňky imunologie   metabolismus   MeSH
• transplantace kostní dřeně MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

A decrease in the abundance and biodiversity of intestinal bacteria within the Firmicutes phylum has been associated with inflammatory bowel disease (IBD). In particular, the anti-inflammatory bacterium Faecalibacterium prausnitzii, member of the Firmicutes phylum and one of the most abundant species in healthy human colon, is underrepresented in the microbiota of IBD patients. The aim of this study was to investigate the immunomodulatory properties of F. prausnitzii strain A2-165, the biofilm forming strain HTF-F and the extracellular polymeric matrix (EPM) isolated from strain HTF-F. For this purpose, the immunomodulatory properties of the F. prausnitzii strains and the EPM were studied in vitro using human monocyte-derived dendritic cells. Then, the capacity of the F. prausnitzii strains and the EPM of HTF-F to suppress inflammation was assessed in vivo in the mouse dextran sodium sulphate (DSS) colitis model. The F. prausnitzii strains and the EPM had anti-inflammatory effects on the clinical parameters measured in the DSS model but with different efficacy. The immunomodulatory effects of the EPM were mediated through the TLR2-dependent modulation of IL-12 and IL-10 cytokine production in antigen presenting cells, suggesting that it contributes to the anti-inflammatory potency of F. prausnitzii HTF-F. The results show that F. prausnitzii HTF-F and its EPM may have a therapeutic use in IBD.

• MeSH
• antigeny povrchové metabolismus   MeSH
• cytokiny genetika   metabolismus   MeSH
• dendritické buňky imunologie   metabolismus   MeSH
• extracelulární matrix metabolismus   MeSH
• fenotyp MeSH
• forkhead transkripční faktory genetika   metabolismus   MeSH
• genetická transkripce MeSH
• idiopatické střevní záněty etiologie   metabolismus   patologie   MeSH
• kolitida chemicky indukované   genetika   imunologie   metabolismus   mikrobiologie   MeSH
• lymfatické uzliny imunologie   metabolismus   MeSH
• mediátory zánětu metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• myši MeSH
• Ruminococcus metabolismus   ultrastruktura   MeSH
• síran dextranu škodlivé účinky   MeSH
• slezina imunologie   metabolismus   MeSH
• střevní sliznice metabolismus   mikrobiologie   patologie   MeSH
• toll-like receptor 2 genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Sitagliptin is a dipeptidyl peptidase IV (DPP-IV) inhibitor that exerts an anti-hyperglycaemic effect by preventing degradation of glucagon-like peptide 1 with subsequent β-cell stimulation and potential regeneration. We tested whether sitagliptin therapy in symptomatic non-obese diabetic (NOD) mice would lead to changes in the immune cell profile, improve β-cell survival and induce diabetes remission. Flow cytometry analysis of immune cells in the spleen and peripheral lymph nodes, immunohistology of the pancreas and DPP-IV activity were investigated in diabetic NOD mice, either treated or non-treated with sitagliptin, at 0, 7, 14 and 28 days after hyperglycaemia onset, and in non-diabetic NOD controls. While compared to diabetic controls sitagliptin prevented increase of the CD8+/CD4+ ratio in pancreatic nodes after four weeks (0.443 ± 0.067 vs. 0.544 ± 0.131; P < 0.05), the population of Tregs in lymph nodes increased from day 0 to 28 in both treated and non-treated diabetic groups (8 ± 1.76 vs. 13.45 ± 5.07 % and 8 ± 1.76 vs. 13.19 ± 5.58 %, respectively). The severity of islet infiltration was similar in both diabetic groups and decreased in parallel with β-cell loss. Surprisingly, sitagliptin blocked the DPP-IV activity only temporarily (on day 7, 277.68 ± 89.2 vs. 547.40 ± 94.04 ng/ml in the diabetic control group) with no apparent effect later on. In conclusion, sitagliptin administered after the onset of overt hyperglycaemia in NOD mice had only a marginal immunological effect and did not lead to diabetes remission. Failure to block DPP-IV over time represents an important finding that requires further explanation.

• MeSH
• časové faktory MeSH
• diabetes mellitus 1. typu farmakoterapie   imunologie   patologie   MeSH
• dipeptidylpeptidasa 4 účinky léků   MeSH
• inhibitory dipeptidylpeptidasy 4 krev   farmakologie   terapeutické užití   MeSH
• Langerhansovy ostrůvky imunologie   patologie   MeSH
• lymfatické uzliny účinky léků   imunologie   patologie   MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední NOD MeSH
• myši MeSH
• pyraziny farmakologie   terapeutické užití   MeSH
• slezina imunologie   patologie   MeSH
• T-lymfocyty - podskupiny účinky léků   imunologie   patologie   MeSH
• triazoly farmakologie   terapeutické užití   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Lymfangioleiomyomatóza (LAM) je zriedkavé ochorenie vyskytujúce sa u žien v reprodukčnom veku. LAM je charakterizovaná abnormálnou proliferáciou nezrelých buniek hladkého svalu. Progresívne ochorenie postihuje najmä pľúcny parenchým a môže mať až fatálny koniec. Mimopľúcna forma LAM sa najčastejšie prejavuje bolesťou brucha, nádormi v retroperitoneu a chylóznym ascitom. V kazuistikách opisujeme výskyt dvoch prípadov mimopľúcnej formy LAM. V obidvoch prípadoch išlo o pelvickú lokalizáciu nádorov v oblasti fossa obturatoria a vasa iliaca externa. Pacientky boli po operácii primárne liečené gestagénmi. Sirolimus bol liekom druhej línie.

Lymphangioleiomyomatosis (LAM) is a rare progressive disease affecting women of childbearing age. The disease is characterised by an abnormal proliferation of immature smooth muscle cells predominantly in the lung. It gradually leads to respiratory failure, and it frequently result in death. Extrapulmonary LAM typically presents with abdominal mass, abdominal pain and chylous ascites. In the case reports we describe two cases of premenopausal females with extrapulmonary LAM. In both cases they occur in pelvic location in the obturator fossa and around the external iliac artery. After surgical procedures patients were primary treated with progesterone. Sirolimus was second-line drugs.

• Klíčová slova
• Rapamun, Plaquenil, Megace,
• MeSH
• chylózní ascites diagnóza   farmakoterapie   terapie   MeSH
• diferenciální diagnóza MeSH
• dospělí MeSH
• drenáž MeSH
• lidé MeSH
• lymfangioleiomyomatóza * diagnóza   terapie   MeSH
• lymfatické uzliny chirurgie   imunologie   mikrobiologie   MeSH
• megestrol terapeutické užití   MeSH
• nádory dělohy MeSH
• nádory vaječníků MeSH
• retroperitoneální nádory MeSH
• sirolimus terapeutické užití   MeSH
• vzácné nemoci diagnóza   farmakoterapie   terapie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

Artiodactyls possess GALT that appears in fetal life and is located at the extreme end of the ileum. These IPP contain mostly B cells and involute early in postnatal life. Rabbits have a similarly located lymphoid organ, called the sacculus rotundus. Studies in sheep and rabbits have led to the concept that the lower hindgut GALT represents primary lymphoid tissue for B cells and is necessary for normal B cell development, analogous to the bursa of Fabricius. This review traces the history of the observations and theories that have led to the existing concept concerning the role of lower GALT. We then review recent data from piglets with resected IPP that challenges the concept that the IPP is primary B cell lymphoid tissue and that artiodactyls and rabbits are members of the GALT group in the same context as gallinaceous birds. Eliminating the IPP as the primary lymphoid tissue for B cells leads to the hypothesis that the IPP acts as first-responder mucosal lymphoid tissue.

• MeSH
• apoptóza MeSH
• Artiodactyla imunologie   MeSH
• B-lymfocyty cytologie   imunologie   MeSH
• buněčný rodokmen MeSH
• bursa Fabricii cytologie   imunologie   chirurgie   MeSH
• druhová specificita MeSH
• gnotobiologické modely MeSH
• imunitní systém embryologie   růst a vývoj   MeSH
• králíci imunologie   MeSH
• kur domácí imunologie   MeSH
• lidé MeSH
• lymfatické uzliny cytologie   imunologie   MeSH
• lymfoidní tkáň cytologie   imunologie   chirurgie   MeSH
• lymfopoéza MeSH
• mezenterium imunologie   MeSH
• modely imunologické MeSH
• Peyerovy pláty cytologie   imunologie   chirurgie   MeSH
• prasata imunologie   MeSH
• savci embryologie   imunologie   MeSH
• střeva imunologie   MeSH
• střevní sliznice embryologie   růst a vývoj   imunologie   MeSH
• tvorba protilátek MeSH
• zvířata MeSH
• Check Tag
• králíci imunologie   MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Mouse polyomavirus (MPyV) VP1-pseudocapsids carrying enhanced green fluorescent protein (EGFP-VLPs) were used for intranasal immunization of mice. EGFP-VLPs induced strong anti-VP1 but not anti-EGFP antibody production. In vitro restimulation with antigen-pulsed bone marrow-derived dendritic cells (BMDCs) induced remarkable T-cell proliferative response specific for both VP1 and EGFP antigen and IL-2 and IFN-gamma production. Surprisingly, no specific cytotoxic activities against VP1 and EGFP proteins were detected. After intranasal administration of EGFP-VLPs, as well as after polyomavirus infection, a moderate reduction of CD4(+)CD25(+)Foxp3(+) T cells was observed in spleens but not in lymph nodes and peripheral blood, suggesting that both MPyV virions and pseudocapsids are able to induce changes in distribution of regulatory T cells. Treatment of EGFP-VLPs pulsed BMDCs with inhibitors of endosomal acidification proved that presentation of peptides on MHCgp class II is dependent on acidic endosomal environment. Substantial decrease of CD4-specific T-cell proliferation in the presence of proteasome inhibitor suggests that MHCgp class II might load VPL-derived peptides processed by proteasomes. Thus, polyomavirus derived VLPs appear to be promising delivery and adjuvant vehicles for therapeutic proteins.

• MeSH
• aplikace intranazální MeSH
• cytotoxické T-lymfocyty imunologie   MeSH
• cytotoxické testy imunologické MeSH
• financování organizované MeSH
• interferon gama biosyntéza   MeSH
• interleukin-2 biosyntéza   MeSH
• krev imunologie   MeSH
• lymfatické uzliny imunologie   MeSH
• myši MeSH
• Polyomavirus imunologie   MeSH
• proliferace buněk MeSH
• protilátky virové krev   MeSH
• rekombinantní fúzní proteiny aplikace a dávkování   imunologie   MeSH
• slezina imunologie   MeSH
• T-lymfocyty - podskupiny imunologie   MeSH
• T-lymfocyty imunologie   MeSH
• vakcíny VLP aplikace a dávkování   imunologie   MeSH
• virové plášťové proteiny aplikace a dávkování   imunologie   MeSH
• zelené fluorescenční proteiny imunologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH