BACKGROUND: The mammalian Leukocyte Receptor Complex (LRC) chromosomal region may contain gene families for the killer cell immunoglobulin-like receptor (KIR) and/or leukocyte immunoglobulin-like receptor (LILR) collections as well as various framing genes. This complex region is well described in humans, mice, and some domestic animals. Although single KIR genes are known in some Carnivora, their complements of LILR genes remain largely unknown due to obstacles in the assembly of regions of high homology in short-read based genomes. METHODS: As part of the analysis of felid immunogenomes, this study focuses on the search for LRC genes in reference genomes and the annotation of LILR genes in Felidae. Chromosome-level genomes based on single-molecule long-read sequencing were preferentially sought and compared to representatives of the Carnivora. RESULTS: Seven putatively functional LILR genes were found across the Felidae and in the Californian sea lion, four to five genes in Canidae, and four to nine genes in Mustelidae. They form two lineages, as seen in the Bovidae. The ratio of functional genes for activating LILRs to inhibitory LILRs is slightly in favor of inhibitory genes in the Felidae and the Canidae; the reverse is seen in the Californian sea lion. This ratio is even in all of the Mustelidae except the Eurasian otter, which has a predominance of activating LILRs. Various numbers of LILR pseudogenes were identified. CONCLUSIONS: The structure of the LRC is rather conservative in felids and the other Carnivora studied. The LILR sub-region is conserved within the Felidae and has slight differences in the Canidae, but it has taken various evolutionary paths in the Mustelidae. Overall, the process of pseudogenization of LILR genes seems to be more frequent for activating receptors. Phylogenetic analysis found no direct orthologues across the Carnivora which corroborate the rapid evolution of LILRs seen in mammals.

• Klíčová slova
• KIR, LILR, Leukocyte Receptor Complex, carnivora, felids, long-read sequencing,
• MeSH
• Canidae * MeSH
• Carnivora * genetika   MeSH
• Felidae * MeSH
• fylogeneze MeSH
• genomika MeSH
• lachtani * MeSH
• leukocyty MeSH
• lidé MeSH
• Mustelidae * MeSH
• myši MeSH
• receptory imunologické genetika   MeSH
• receptory KIR genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• receptory imunologické MeSH
• receptory KIR MeSH

Due to production of special homodimeric heavy chain antibodies, somatic hypermutation of their T-cell receptor genes and unusually low diversity of their major histocompatibility complex genes, camels represent an important model for immunogenetic studies. Here, we analyzed genes encoding selected natural killer cell receptors with a special focus on genes encoding receptors for major histocompatibility complex (MHC) class I ligands in the two domestic camel species, Camelus dromedarius and Camelus bactrianus. Based on the dromedary genome assembly CamDro2, we characterized the genetic contents, organization, and variability of two complex genomic regions, the leukocyte receptor complex and the natural killer complex, along with the natural cytotoxicity receptor genes NCR1, NCR2, and NCR3. The genomic organization of the natural killer complex region of camels differs from cattle, the phylogenetically most closely related species. With its minimal set of KLR genes, it resembles this complex in the domestic pig. Similarly, the leukocyte receptor complex of camels is strikingly different from its cattle counterpart. With KIR pseudogenes and few LILR genes, it seems to be simpler than in the pig. The syntenies and protein sequences of the NCR1, NCR2, and NCR3 genes in the dromedary suggest that they could be human orthologues. However, only NCR1 and NCR2 have a structure of functional genes, while NCR3 appears to be a pseudogene. High sequence similarities between the two camel species as well as with the alpaca Vicugna pacos were observed. The polymorphism in all genes analyzed seems to be generally low, similar to the rest of the camel genomes. This first report on natural killer cell receptor genes in camelids adds new data to our understanding of specificities of the camel immune system and its functions, extends our genetic knowledge of the innate immune variation in dromedaries and Bactrian camels, and contributes to studies of natural killer cell receptors evolution in mammals.

• Klíčová slova
• SNP, camelid, leukocyte receptor complex, microsatellites, natural killer complex,
• Publikační typ
• časopisecké články MeSH

The adaptive immune response critically hinges on the functionality of T cell receptors, governed by complex molecular mechanisms, including ubiquitination. In this study, we delved into the role of in T cell immunity, focusing on T cell-B cell conjugate formation and T cell activation. Using a CRISPR-Cas9 screening approach targeting deubiquitinases genes in Jurkat T cells, we identified BAP1 as a key positive regulator of T cell-B cell conjugate formation. Subsequent investigations into BAP1 knockout cells revealed impaired T cell activation, evidenced by decreased MAPK and NF-kB signaling pathways and reduced CD69 expression upon T cell receptor stimulation. Flow cytometry and qPCR analyses demonstrated that BAP1 deficiency leads to decreased surface expression of T cell receptor complex components and reduced mRNA levels of the co-stimulatory molecule CD28. Notably, the observed phenotypes associated with BAP1 knockout are specific to T cells and fully dependent on BAP1 catalytic activity. In-depth RNA-seq and mass spectrometry analyses further revealed that BAP1 deficiency induces broad mRNA and protein expression changes. Overall, our findings elucidate the vital role of BAP1 in T cell biology, especially in T cell-B cell conjugate formation and T cell activation, offering new insights and directions for future research in immune regulation.

• Klíčová slova
• BAP1, CRISPR-Cas9 screening, T cell activation, T cell receptor (TCR), T cell-B cell conjugates,
• MeSH
• aktivace lymfocytů * imunologie   MeSH
• B-lymfocyty * imunologie   metabolismus   MeSH
• Jurkat buňky MeSH
• lidé MeSH
• nádorové supresorové proteiny * metabolismus   genetika   MeSH
• receptory antigenů T-buněk * metabolismus   MeSH
• signální transdukce MeSH
• T-lymfocyty * imunologie   metabolismus   MeSH
• thiolesterasa ubikvitinu * genetika   metabolismus   nedostatek   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• BAP1 protein, human MeSH Prohlížeč
• nádorové supresorové proteiny * MeSH
• receptory antigenů T-buněk * MeSH
• thiolesterasa ubikvitinu * MeSH

OBJECTIVE: The receptor for advanced glycation end products, RAGE, has been implicated in pathogenesis of many diseases. Soluble RAGE, sRAGE, extracellular domain of RAGE, is new biomarker. The aim of the study was to determine sRAGE levels in physiological pregnancy and their changes in pregnancies complicated by preterm labor or preeclampsia. DESIGN AND METHODS: Serum levels of sRAGE were determined in 79 healthy pregnant women, 42 pregnant women in preterm labor or with preeclampsia and 24 non-pregnant controls. RESULTS: sRAGE serum levels are decreased in physiological pregnancy compared to healthy non-pregnant controls (p<0.001). Serum sRAGE concentrations are higher in the 2nd trimester of physiological pregnancy, compared to the 1st and 3rd trimesters of pregnancy (p<0.001). sRAGE levels in women with preterm labor are decreased (p<0.05) and correlate negatively with the leukocyte count (r=-0.47, p<0.05). In women with preeclampsia, sRAGE is elevated (p<0.05) and correlates with serum creatinine concentration (r=0.54, p<0.05) and with uric acid concentration (r=0.51, p<0.05). CONCLUSION: Our results clearly demonstrate significant differences in serum sRAGE levels in physiological pregnancy and in pathological states in pregnancy, however, further studies are required demonstrate the usefulness and significance of sRAGE.

• MeSH
• dospělí MeSH
• lidé MeSH
• předčasná porodní činnost krev   MeSH
• preeklampsie krev   MeSH
• receptor pro konečné produkty pokročilé glykace MeSH
• receptory imunologické krev   MeSH
• rozpustnost MeSH
• těhotenství MeSH
• trimestry těhotenství krev   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• receptor pro konečné produkty pokročilé glykace MeSH
• receptory imunologické MeSH

BACKGROUND AND AIMS: Intestinal inflammation in inflammatory bowel diseases [IBD] is thought to be T cell mediated and therefore dependent on the interaction between the T cell receptor [TCR] and human leukocyte antigen [HLA] proteins expressed on antigen presenting cells. The collection of all TCRs in one individual, known as the TCR repertoire, is characterised by enormous diversity and inter-individual variability. It was shown that healthy monozygotic [MZ] twins are more similar in their TCR repertoire than unrelated individuals. Therefore MZ twins, concordant or discordant for IBD, may be useful to identify disease-related and non-genetic factors in the TCR repertoire which could potentially be used as disease biomarkers. METHODS: Employing unique molecular barcoding that can distinguish between polymerase chain reaction [PCR] artefacts and true sequence variation, we performed deep TCRα and TCRβ repertoire profiling of the peripheral blood of 28 MZ twin pairs from Denmark and Germany, 24 of whom were discordant and four concordant for IBD. RESULTS: We observed disease- and smoking-associated traits such as sharing, diversity and abundance of specific clonotypes in the TCR repertoire of IBD patients, and particularly in patients with active disease, compared with their healthy twins. CONCLUSIONS: Our findings identified TCR repertoire features specific for smokers and IBD patients, particularly when signs of disease activity were present. These findings are a first step towards the application of TCR repertoire analyses as a valuable tool to characterise inflammatory bowel diseases and to identify potential biomarkers and true disease causes.

• Klíčová slova
• T cell receptor [TCR] repertoire, inflammatory bowel diseases [IBD], monozygotic twins,
• MeSH
• C-reaktivní protein analýza   MeSH
• Crohnova nemoc * diagnóza   imunologie   patofyziologie   MeSH
• dospělí MeSH
• dvojčata monozygotní MeSH
• feces MeSH
• geny TcR alfa * MeSH
• geny TcR beta * MeSH
• kouření imunologie   MeSH
• leukocytární L1-antigenní komplex analýza   MeSH
• lidé MeSH
• posouzení stavu pacienta MeSH
• receptory antigenů T-buněk alfa-beta krev   MeSH
• sekvenční analýza DNA MeSH
• ulcerózní kolitida * diagnóza   imunologie   patofyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• studie na dvojčatech MeSH
• Geografické názvy
• Dánsko MeSH
• Německo MeSH
• Názvy látek
• C-reaktivní protein MeSH
• leukocytární L1-antigenní komplex MeSH
• receptory antigenů T-buněk alfa-beta MeSH

Following nerve injury, disintegrated axonal mitochondria distal to the injury site release mitochondrial formylated peptides and DNA that can induce activation and inflammatory profiling of Schwann cells via formyl peptide receptor 2 (Fpr2) and toll-like receptor 9 (TLR9), respectively. We studied RT4 schwannoma cells to investigate the regulation of Fpr2 and TLR9 after stimulation with fMLF as a prototypical formylated peptide. RT4 cells were treated with fMLF at various concentrations and times with and without pretreatment with inhibitors (chloroquine for activated TLR9, PBP10 for Fpr2). Western blots of Fpr2, TLR9, p-p38, p-NFκB, and IL-6 were compared in relation to inflammatory profiling of RT4 cells and chemokine receptors (CCR2, CXCR4) as potential co-receptors of Fpr2. fMLF stimulation upregulated Fpr2 in RT4 cells at low concentrations (10 nM and 100 nM) but higher concentrations were required (10 µM and 50 µM) when the cells were pretreated with an activated TLR9 inhibitor. Moreover, the higher concentrations of fMLF could modulate TLR9 and inflammatory markers. Upregulation of Fpr2 triggered by 10 nM and 100 nM fMLF coincided with higher levels of chemokine receptors (CCR2, CXCR4) and PKCβ. Treating RT4 cells with fMLF, as an in vitro model of Schwann cells, uncovered Schwann cells' complex responses to molecular patterns of release from injured axonal mitochondria.

• Klíčová slova
• Wallerian degeneration, chemokines, cytokines, damage-associated molecular patterns, disintegration, mitochondria, receptors,
• MeSH
• chlorochin farmakologie   MeSH
• krysa rodu Rattus MeSH
• N-formylmethionin-leucyl-fenylalanin farmakologie   MeSH
• nádorové buněčné linie MeSH
• neurilemom metabolismus   patologie   MeSH
• receptory CCR2 genetika   metabolismus   MeSH
• receptory CXCR4 genetika   metabolismus   MeSH
• receptory pro formylované peptidy antagonisté a inhibitory   genetika   metabolismus   MeSH
• Schwannovy buňky cytologie   účinky léků   metabolismus   MeSH
• signální transdukce účinky léků   MeSH
• toll-like receptor 9 antagonisté a inhibitory   genetika   metabolismus   MeSH
• upregulace účinky léků   MeSH
• zánět metabolismus   patologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• chlorochin MeSH
• N-formylmethionin-leucyl-fenylalanin MeSH
• receptory CCR2 MeSH
• receptory CXCR4 MeSH
• receptory pro formylované peptidy MeSH
• toll-like receptor 9 MeSH

Presence of functional immune system is critical for any attempt aimed at improving survival of breast cancer patients by strategies based on immune system manipulation. We evaluated by flow cytometry the phenotype of peripheral blood leukocyte of 43 breast cancer patients. In 11 patients, the phenotype was evaluated before and during the chemotherapy by combination of doxorubicin and paclitaxel (AT). Compared with controls breast cancer patients had significantly higher relative and absolute numbers of CD3 HLA-DR+, CD3+CD69+ and CD14+CD16+, and significantly lower percentages of CD3 and CD8+CD28+ cells. After one cycle of AT, the absolute numbers of CD3 , CD3+CD4+, CD3+CD8+ and CD8+CD28+ cells increased significantly. Present data show a presence of T-cell activation in breast cancer patients. Administration of AT may lead to an increase in functional T-cells in peripheral blood, indicating a potential for combining chemotherapy with immunotherapy in the treatment of breast cancer patients.

• MeSH
• antigeny CD14 metabolismus   MeSH
• antigeny CD28 metabolismus   MeSH
• antigeny CD3 metabolismus   MeSH
• CD antigeny metabolismus   MeSH
• CD4-pozitivní T-lymfocyty imunologie   MeSH
• CD8-pozitivní T-lymfocyty imunologie   MeSH
• diferenciační antigeny T-lymfocytů metabolismus   MeSH
• dospělí MeSH
• doxorubicin aplikace a dávkování   MeSH
• HLA-DR antigeny metabolismus   MeSH
• imunofenotypizace MeSH
• lektiny typu C MeSH
• leukocyty imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory prsu krev   farmakoterapie   imunologie   MeSH
• paclitaxel aplikace a dávkování   MeSH
• podskupiny lymfocytů imunologie   MeSH
• protokoly antitumorózní kombinované chemoterapie terapeutické užití   MeSH
• receptory IgG metabolismus   MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny CD14 MeSH
• antigeny CD28 MeSH
• antigeny CD3 MeSH
• CD antigeny MeSH
• CD69 antigen MeSH Prohlížeč
• diferenciační antigeny T-lymfocytů MeSH
• doxorubicin MeSH
• HLA-DR antigeny MeSH
• lektiny typu C MeSH
• paclitaxel MeSH
• receptory IgG MeSH

The purpose of the study was to describe and compare normal and 5-fluorouracil (5-FU)-suppressed hematopoiesis in adenosine A(3) receptor knock-out (A(3)AR KO) mice and their wild-type (WT) counterparts. To meet the purpose, a complex hematological analysis comprising nineteen peripheral blood and bone marrow parameters was performed in the mice. Defects previously observed in the peripheral blood erythrocyte and thrombocyte parameters of the A(3)AR KO mice were confirmed. Compartments of the bone marrow progenitor cells for granulocytes/macrophages and erythrocytes were enhanced in the control, as well as in the 5-FU-administered A(3)AR KO mice. 5-FU-induced hematopoietic suppression, evaluated on day 2 after the administration of the cytotoxic drug, was found to be significantly deeper in the A(3)AR KO mice compared with their WT counterparts, as measured at the level of the bone marrow progenitor cells. The rate of regeneration, as assessed between days 2 and 7 after 5-FU administration, was observed in the population of the granulocyte/macrophage progenitor cells to be higher in the A(3)AR KO mice in comparison with the WT ones. The increased depth of 5-FU-induced suppression in the compartments of the hematopoietic progenitor cells in the A(3)AR KO mice represents probably a hitherto undescribed further consequence of the lack of adenosine A(3) receptors and indicates its synergism with the pharmacologically induced cytotoxic action of 5-FU.

• MeSH
• antimetabolity antitumorózní farmakologie   MeSH
• biochemická analýza krve MeSH
• buňky kostní dřeně účinky léků   MeSH
• fluorouracil farmakologie   MeSH
• hematopoéza účinky léků   MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• myši MeSH
• počet erytrocytů MeSH
• počet leukocytů MeSH
• receptor adenosinový A3 genetika   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antimetabolity antitumorózní MeSH
• fluorouracil MeSH
• receptor adenosinový A3 MeSH

Anti-Iatk monoclonal antibodies (mAbs) were found to inhibit syngeneic mixed lymphocyte reaction (SMLR) of mice with k and a haplotypes (H-2k and H-2a) of the major histocompatibility complex (MHC) by acting on responder T cells but not stimulator cells. Only the early phase of SMLR was inhibited by anti-Iat mAbs. The inhibitory effect was due to the blocking of autoreactive T cells but not induction of suppressor lymphocytes. Cross-linking of Iat epitopes induced T cell proliferation of k haplotype strain. The inhibitory pattern of SMLR by four anti-Iat mAbs varied among different strains of mice. The inhibitory pattern seemed to depend on MHC and unidentified non-MHC background genes possessed by stimulator cells, suggesting that the shape of the MHC recognition site must have different conformation depending on both MHC and non-MHC gene products recognized. However, the inhibitory pattern of SMLR by anti-Iat mAbs of strains which differ at the I-J locus: B10.A(5R) and B10.A(3R) was dependent on the genotype of stimulator cells. The same was observed in B10.S(9R) and B10.HTT strains. The inhibitory activity of anti-Iat mAbs was entirely directed against responder T cells and was not passively carried out by the stimulators. It was concluded that Iat epitopes are I region controlled determinants that are utilized by T cells as receptors for self Ia antigens. It is suggested that anti-Iat mAbs react with an idiotype on the receptor(s) for Ia or I-J, or possibly a "receptor" for these receptors.

• MeSH
• aktivace lymfocytů MeSH
• epitopy imunologie   MeSH
• H-2 antigeny imunologie   MeSH
• histokompatibilita - antigeny třídy II imunologie   MeSH
• imunologická tolerance * MeSH
• inbrední kmeny myší genetika   imunologie   MeSH
• křížení genetické MeSH
• monoklonální protilátky imunologie   MeSH
• myši MeSH
• receptory antigenů T-buněk * MeSH
• T-lymfocyty imunologie   MeSH
• test smíšené lymfocytární kultury MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• epitopy MeSH
• H-2 antigeny MeSH
• histokompatibilita - antigeny třídy II MeSH
• monoklonální protilátky MeSH
• receptory antigenů T-buněk * MeSH

BACKGROUND: The scavenger receptor for complexes hemoglobin-haptoglobin (CD163), which is expressed on monocytes/ macrophages, is shed to the body fluids in a soluble form (sCD163). OBJECTIVES: To evaluate the dynamics of sCD163 in the blood of patients undergoing cardiac surgery. PATIENTS AND METHODS: Sixty-one adult patients who underwent coronary artery bypass grafting (CABG) were enrolled in the study. They were assigned to undergo CABG using either cardiopulmonary bypass (CPB), "on-pump", (22 patients), modified CPB, mini "on-pump", (17 patients) or without CPB, "off-pump", (22 patients) surgery. Serum levels of sCD163 in venous blood samples taken before and after surgery, and during an early postoperative period, were evaluated by Macro 163(TM) diagnostic kit (IQ Products, Groningen, NL). RESULTS: Compared to the preoperative levels ("on-pump"; 344 ng/mL, "off-pump"; 314.5 ng/mL, mini-invasive "on-pump"; 336.5 ng/mL) serum levels were elevated at the finish of surgery, reaching maximum at the 1(st) postoperative day ("onpump"; 658 ng/mL; p<0.05, "off-pump"; 810.5 ng/mL; p<0.01; mini-invasive "on-pump"; 663 ng/mL; non-significant).No significant differences regarding the serum levels of sCD163 between different surgical approaches were found. CONCLUSION: Serum level of sCD163 scavenger molecule for hemoglobin is elevated at the end of surgery and at the 1(st) postoperative day, being little influenced by cardiopulmonary bypass.

• MeSH
• antigeny diferenciační myelomonocytární krev   MeSH
• CD antigeny krev   MeSH
• haptoglobiny metabolismus   MeSH
• hemoglobiny metabolismus   MeSH
• kardiopulmonální bypass škodlivé účinky   MeSH
• koronární bypass škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• receptory buněčného povrchu krev   MeSH
• senioři MeSH
• zánět krev   etiologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigeny diferenciační myelomonocytární MeSH
• CD antigeny MeSH
• CD163 Antigen MeSH
• haptoglobin-hemoglobin complex MeSH Prohlížeč
• haptoglobiny MeSH
• hemoglobiny MeSH
• receptory buněčného povrchu MeSH