@article{MTMT:34642179, title = {Splenectomy at Early stage of Autoimmune Arthritis Delayed Inflammatory Response and Reduced Joint Deterioration in Mice}, url = {https://m2.mtmt.hu/api/publication/34642179}, author = {Khanfar, Esam and Olasz, Katalin and Gál, Szonja and Gajdócsi, Erzsébet Emília and Kajtár, Béla and Kiss, Tamás and Balogh, Péter and Berki, Tímea and Boldizsár, Ferenc}, doi = {10.1093/cei/uxae013}, journal-iso = {CLIN EXP IMMUNOL}, journal = {CLINICAL AND EXPERIMENTAL IMMUNOLOGY}, unique-id = {34642179}, issn = {0009-9104}, abstract = {The spleen plays a role in innate- and adaptive immunity, and autoimmune diseases like rheumatoid arthritis (RA). We investigated the effect of splenectomy in early and moderate stages of autoimmune arthritis in a mouse model. To induce recombinant human G1-induced arthritis (GIA), BALB/c mice were immunized intraperitoneally three times in 4 weeks interval with the rhG1 antigen. Mice were splenectomized on day 7 (SPE1) or day 35 (SPE2) after the initiation of immunization, and were tested for clinical severity, joint radiological- and histological changes, serum levels of inflammatory cytokines and autoantibodies, and rhG1-specific immune responses, and compared to those in control mice with spleen left intact. Circulating Tregs and T-helper subset ratios in the spleen and inguinal lymph nodes were also examined using flow cytometry. The onset of severe inflammatory response was significantly delayed in SPE1 and SPE2 groups compared to control mice at early stages of GIA, which was associated with increased circulating Tregs. After the third immunization, as disease progressed, the severity scores were robustly increased in all mice. Nevertheless, in splenectomized mice, we observed reduced joint deterioration and cartilage damage, more Th2 cells in lymph nodes, and reduced levels of pro-inflammatory cytokines and autoantibodies in their sera. Mesenteric lymph node cells of splenectomized mice exhibited weaker response in vitro against the rhG1 antigen compared to control mice spleen. In conclusion, splenectomy in early stages of GIA delayed the inflammatory response, suggesting a protective effect against the development and progression of severe destructive arthritis.}, keywords = {Cytokines; splenectomy; Treg; Autoimmune arthritis}, year = {2024}, eissn = {1365-2249}, orcid-numbers = {Khanfar, Esam/0000-0001-5260-7937; Kajtár, Béla/0000-0001-5551-3709; Berki, Tímea/0000-0002-0134-8127} } @article{MTMT:34430281, title = {Quantitative Analysis of NKX2-3 Expression in Human Colon : An Immunohistochemical Study}, url = {https://m2.mtmt.hu/api/publication/34430281}, author = {Gábris, Fanni and Kajtár, Béla and Kellermayer, Zoltán and Balogh, Péter}, doi = {10.1369/00221554231217336}, journal-iso = {J HISTOCHEM CYTOCHEM}, journal = {JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY}, volume = {72}, unique-id = {34430281}, issn = {0022-1554}, abstract = {In mice, Nkx2-3 homeodomain transcription factor defines the vascular specification of secondary and tertiary lymphoid tissues of the intestines. In human studies, polymorphisms in NKX2-3 have been identified as a susceptibility factor in inflammatory bowel diseases, whereas in mice, its absence is associated with protection against experimental colitis and enhanced intestinal epithelial proliferation. Here, we investigated the expression of NKX2-3 in normal, polyp, and adenocarcinoma human colon samples using immunohistochemistry and quantitative morphometry, correlating its expression with endothelial and mesenchymal stromal markers. Our results revealed that the expression of NKX2-3 is regionally confined to the lamina propria and lamina muscularis mucosae, and its production is restricted mostly to endothelial cells and smooth muscle cells with variable co-expression of CD34, alpha smooth muscle antigen (αSMA), and vascular adhesion protein-1 (VAP-1). The frequency of NKX2-3-positive cells and intensity of expression correlated inversely with aging. Furthermore, in most colorectal carcinoma samples, we observed a significant reduction of NKX2-3 expression. These findings indicate that the NKX2-3 transcription factor is produced by both endothelial and non-endothelial tissue constituents in the colon, and its expression changes during aging and in colorectal malignancies. (J Histochem Cytochem XX: XXX-XXX, XXXX).}, keywords = {COLON; ENDOTHELIUM; Adenocarcinoma; stroma; polyp; Nkx2-3}, year = {2024}, eissn = {1551-5044}, pages = {11-23}, orcid-numbers = {Gábris, Fanni/0000-0002-6036-3941; Kajtár, Béla/0000-0001-5551-3709} } @article{MTMT:34050798, title = {Natural and Pathological Autoantibodies Show Age-Related Changes in a Spontaneous Autoimmune Mouse (NZB) Model}, url = {https://m2.mtmt.hu/api/publication/34050798}, author = {Gál, Szonja and Gajdócsi, Erzsébet Emília and Khanfar, Esam and Olasz, Katalin and Simon, Diána and Balogh, Péter and Berki, Tímea and Németh, Péter and Boldizsár, Ferenc}, doi = {10.3390/ijms24129809}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {24}, unique-id = {34050798}, issn = {1661-6596}, abstract = {The natural autoantibody (natAAb) network is thought to play a role in immune regulation. These IgM antibodies react with evolutionary conserved antigens; however, they do not lead to pathological tissue destruction as opposed to pathological autoantibodies (pathAAb). The exact relation between the natAAbs and pathAAbs is still not completely understood; therefore, in the present study, we set out to measure nat- and pathAAb levels against three conserved antigens in a spontaneous autoimmune disease model: the NZB mouse strain which develops autoimmune hemolytic anemia (AIHA) from six months of age. There was an age dependent increase in the natAAb levels in the serum against Hsp60, Hsp70, and the mitochondrial citrate synthase until 6-9 months of age, followed by a gradual decrease. The pathological autoantibodies appeared after six months of age, which corresponded with the appearance of the autoimmune disease. The changes in nat/pathAAb levels were coupled with decreasing B1- and increasing plasma cell and memory B cell percentages. Based on this, we propose that there is a switch from natAAbs towards pathAAbs in aged NZB mice.}, keywords = {autoimmune disease; natural autoantibody; pathological autoantibody}, year = {2023}, eissn = {1422-0067}, orcid-numbers = {Khanfar, Esam/0000-0001-5260-7937; Berki, Tímea/0000-0002-0134-8127} } @article{MTMT:33775153, title = {Absence of Nkx2-3 induces ectopic lymphatic endothelial differentiation associated with impaired extramedullary stress hematopoiesis in the spleen.}, url = {https://m2.mtmt.hu/api/publication/33775153}, author = {Gábris, Fanni and Kiss, Gabriella and Szirmay, Balázs and Szomor, Árpád and Berta, Gergely and Jakus, Zoltán and Kellermayer, Zoltán and Balogh, Péter}, doi = {10.3389/fcell.2023.1170389}, journal-iso = {FRONT CELL DEV BIOL}, journal = {FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY}, volume = {11}, unique-id = {33775153}, issn = {2296-634X}, abstract = {The red and white pulps as two main parts of the spleen are arranged around distinct types of vasculature, and perform significantly different functions in both humans and mice. Previous observations indicated a profound alteration of the local vessel specialization in mice lacking Nkx2-3 homeodomain transcription factor, including contradictory results suggesting presence of an ectopic lymphatic vascular structure. Furthermore, how the absence of Nkx2-3 and the consequential changes in endothelial components affect the extramedullary hematopoietic activity restricted to the splenic red pulp is unknown. In this work, we investigated the role of Nkx2-3 homeodomain transcription factor as a major morphogenic determinant for vascular specification, and its effect in the extramedullary hematopoiesis following acute blood loss and pharmacological stimulation of megakaryocyte differentiation after treatment with thrombopoietin-receptor mimetic Romiplostim. We found that, in mice lacking Nkx2-3, Prox1-positive lymphatic capillaries containing gp38/CD31 double positive lymphatic endothelial cells develop, arranged into an extensive meshwork, while the Clever1-positive venous segments of red pulp blood vasculature are absent. This lymphatic endothelial shift is coupled with a severely compromised splenic erythropoiesis and a significantly reduced splenic megakaryocyte colony formation following Romiplostim treatment in mice lacking Nkx2-3. These findings indicate that the shift of microvascular patterning in the absence of Nkx2-3 includes the emergence of ectopic Prox1-positive lymphatic vessels, and that this pivoting towards lymph node-like vascular patterning is associated with an impaired reserve hematopoietic capacity of the splenic red pulp.}, keywords = {SPLEEN; stroma; Hematopoiesis; Prox1; Nkx2-3; Lymphatic endothelium}, year = {2023}, eissn = {2296-634X}, orcid-numbers = {Gábris, Fanni/0000-0002-6036-3941; Jakus, Zoltán/0000-0002-6304-2369} } @{MTMT:33718259, title = {A gasztrointesztinális traktus immunológiája}, url = {https://m2.mtmt.hu/api/publication/33718259}, author = {Balogh, Péter and Pós, Zoltán}, booktitle = {Gasztroenterológia}, unique-id = {33718259}, year = {2023}, pages = {94-113}, orcid-numbers = {Pós, Zoltán/0000-0002-2574-7616} } @article{MTMT:33695779, title = {The miR-20a/miR-92b Profile Is Associated with Circulating γδ T-Cell Perturbations in Mild Psoriasis}, url = {https://m2.mtmt.hu/api/publication/33695779}, author = {Tokić, Stana and Jirouš, Maja and Plužarić, Vera and Mihalj, Martina and Šola, Marija and Tolušić Levak, Maja and Glavaš, Kristina and Balogh, Péter and Štefanić, Mario}, doi = {10.3390/ijms24054323}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {24}, unique-id = {33695779}, issn = {1661-6596}, abstract = {Psoriasis vulgaris (PV) is an autoinflammatory dermatosis of unknown etiology. Current evidence suggests a pathogenic role of γδT cells, but the growing complexity of this population has made the offending subset difficult to pinpoint. The work on γδTCRint and γδTCRhi subsets, which express intermediate and high levels of γδTCR at their surface, respectively, is particularly scarce, leaving their inner workings in PV essentially unresolved. We have shown here that the γδTCRint/γδTCRhi cell composition and their transcriptom are related to the differential miRNA expression by performing a targeted miRNA and mRNA quantification (RT-qPCR) in multiplexed, flow-sorted γδ blood T cells from healthy controls (n = 14) and patients with PV (n = 13). A significant loss of miR-20a in bulk γδT cells (~fourfold decrease, PV vs. controls) largely mirrored increasing Vδ1-Vδ2- and γδintVδ1-Vδ2- cell densities in the bloodstream, culminating in a relative excess of γδintVδ1-Vδ2- cells for PV. Transcripts encoding DNA-binding factors (ZBTB16), cytokine receptors (IL18R1), and cell adhesion molecules (SELPLG) were depleted in the process, closely tracking miR-20a availability in bulk γδ T-cell RNA. Compared to controls, PV was also associated with enhanced miR-92b expression (~13-fold) in bulk γδT cells that lacked association with the γδT cell composition. The miR-29a and let-7c expressions remained unaltered in case-control comparisons. Overall, our data expand the current landscape of the peripheral γδT cell composition, underlining changes in its mRNA/miRNA transcriptional circuits that may inform PV pathogenesis.}, keywords = {psoriasis vulgaris; γδ T cells; hsa-let-7c; hsa-mir-20a; hsa-mir-29a; hsa-mir-92b}, year = {2023}, eissn = {1422-0067} } @article{MTMT:33425281, title = {Öregedéshez társult B-sejtek (ABC): eredet, jellemzők és immunpatológiai szerepeik}, url = {https://m2.mtmt.hu/api/publication/33425281}, author = {Balogh, Péter}, journal-iso = {IMMUNOLÓGIAI SZEMLE}, journal = {IMMUNOLÓGIAI SZEMLE}, volume = {14}, unique-id = {33425281}, issn = {2061-0203}, year = {2022}, pages = {27-32} } @article{MTMT:33293947, title = {An NKX-COUP-TFII morphogenetic code directs mucosal endothelial addressin expression}, url = {https://m2.mtmt.hu/api/publication/33293947}, author = {Dinh, Thanh Theresa and Xiang, Menglan and Rajaraman, Anusha and Wang, Yongzhi and Salazar, Nicole and Zhu, Yu and Roper, Walter and Rhee, Siyeon and Brulois, Kevin and O’Hara, Ed and Kiefel, Helena and Dinh, Truc M. and Bi, Yuhan and Gonzalez, Dalila and Bao, Evan P. and Red-Horse, Kristy and Balogh, Péter and Gábris, Fanni and Gaszner, Balázs and Berta, Gergely and Pan, Junliang and Butcher, Eugene C.}, doi = {10.1038/s41467-022-34991-2}, journal-iso = {NAT COMMUN}, journal = {NATURE COMMUNICATIONS}, volume = {13}, unique-id = {33293947}, issn = {2041-1723}, abstract = {Immunoglobulin family and carbohydrate vascular addressins encoded by Madcam1 and St6gal1 control lymphocyte homing into intestinal tissues, regulating immunity and inflammation. The addressins are developmentally programmed to decorate endothelial cells lining gut post-capillary and high endothelial venules (HEV), providing a prototypical example of organ- and segment-specific endothelial specialization. We identify conserved NKX-COUP-TFII composite elements (NCCE) in regulatory regions of Madcam1 and St6gal1 that bind intestinal homeodomain protein NKX2-3 cooperatively with venous nuclear receptor COUP-TFII to activate transcription. The Madcam1 element also integrates repressive signals from arterial/capillary Notch effectors. Pan-endothelial COUP-TFII overexpression induces ectopic addressin expression in NKX2-3 + capillaries, while NKX2-3 deficiency abrogates expression by HEV. Phylogenetically conserved NCCE are enriched in genes involved in neuron migration and morphogenesis of the heart, kidney, pancreas and other organs. Our results define an NKX-COUP-TFII morphogenetic code that targets expression of mucosal vascular addressins.}, year = {2022}, eissn = {2041-1723}, orcid-numbers = {Xiang, Menglan/0000-0003-4234-4998; Rhee, Siyeon/0000-0002-7642-4016; Red-Horse, Kristy/0000-0003-1541-601X; Gábris, Fanni/0000-0002-6036-3941; Gaszner, Balázs/0000-0003-2830-2732; Pan, Junliang/0000-0002-2373-0917; Butcher, Eugene C./0000-0001-8786-7907} } @article{MTMT:33125064, title = {Global alteration of colonic microRNAome landscape associated with inflammatory bowel disease}, url = {https://m2.mtmt.hu/api/publication/33125064}, author = {Boros, Éva and Hegedűs, Zoltán and Kellermayer, Zoltán and Balogh, Péter and Nagy, István}, doi = {10.3389/fimmu.2022.991346}, journal-iso = {FRONT IMMUNOL}, journal = {FRONTIERS IN IMMUNOLOGY}, volume = {13}, unique-id = {33125064}, issn = {1664-3224}, abstract = {Inflammatory Bowel Disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract that associates with, among others, increased risk of colorectal cancer. There is a growing evidence that miRNAs have important roles in pathological processes, such as inflammation or carcinogenesis. Understanding the molecular mechanisms such as alterations in microRNAome upon chronic intestinal inflammation is critical for understanding the exact pathomechanism of IBD. Hence, we conducted a genome wide microRNAome analysis by applying miRNA-Seq in a rat model of experimental colitis, validated the data by QPCR, examined the expression of a selection of precursor and mature miRNAs, performed in depth biological interpretation using Ingenuity Pathway Analysis and tested the obtained results on samples derived from human patients. We identified specific, interdependent expression pattern of activator/repressor transcription factors, miRNAs and their direct targets in the inflamed colon samples. Particularly, decreased expression of the miR-200 family members (miR-200a/b/c,-141, and -429) and miR-27b correlates with the reduced level of their enhancers (HNF1B, E2F1), elevated expression of their repressors (ZEB2, NFKB1) and increased expression of their target genes (ZEB2, RUNX1). Moreover, the marked upregulation of six miR-27b target genes (IFI16, GCA, CYP1B1, RUNX1, MEF2C and MMP13) in the inflamed colon tissues is a possible direct consequence of the lack of repression due to the downregulated miRNA-27b expression. Our data indicate that changes in microRNAome are associated with the pathophysiology of IBD, consequently, microRNAs offer potential targets for the diagnosis, prognosis and treatment of IBD.}, year = {2022}, eissn = {1664-3224} } @article{MTMT:33029408, title = {Age-Associated B Cell Features of the Murine High-Grade B Cell Lymphoma Bc.DLFL1 and Its Extranodal Expansion in Abdominal Adipose Tissues}, url = {https://m2.mtmt.hu/api/publication/33029408}, author = {Jia, Xinkai and Bene, Judit and Balázs, Noémi and Szabó, Katalin and Berta, Gergely and Herczeg, Róbert and Gyenesei, Attila and Balogh, Péter}, doi = {10.4049/jimmunol.2100956}, journal-iso = {J IMMUNOL}, journal = {JOURNAL OF IMMUNOLOGY}, volume = {208}, unique-id = {33029408}, issn = {0022-1767}, abstract = {Diffuse large B cell lymphoma comprises a heterogeneous group of B cell-derived tumors, with different degrees of aggressiveness, as defined by their cellular origin and tissue microenvironment. Using the spontaneous Bc.DLFL1 lymphoma originating from a BALB/c mouse as a diffuse large B cell lymphoma model, in this study we demonstrate that the lymphoma cells display surface phenotype, IgH V-region somatic mutations, transcription factor characteristics and in vivo location to splenic extrafollicular regions of age-associated B cells (ABCs), corresponding to T-bet(+) and Blimp-1(+)/CD138(-) plasmablasts derivation. The expansion of lymphoma cells within lymphoid tissues took place in a close arrangement with CD11c(+) dendritic cells, whereas the extranodal infiltration occurred selectively in the mesentery and omentum containing resident gp38/podoplanin(+) fibroblastic reticular cells. Antagonizing BAFF-R activity by mBR3-Fc soluble receptor fusion protein led to a significant delay of disease progression. The extranodal expansion of Bc.DLFL1 lymphoma within the omental and mesenteric adipose tissues was coupled with a significant change of the tissue cytokine landscape, including both shared alterations and tissue-specific variations. Our findings indicate that while Bc.DLFL1 cells of ABC origin retain the positioning pattern within lymphoid tissues of their physiological counterpart, they also expand in non-lymphoid tissues in a BAFF-dependent manner, where they may alter the adipose tissue microenvironment to support their extranodal growth.}, keywords = {MODEL; RECEPTOR; TRANSCRIPTION FACTOR; DENDRITIC CELLS; GLYCOPROTEIN; Autoimmunity; Stromal Cells; T-bet; BAFF-R}, year = {2022}, eissn = {1550-6606}, pages = {2866-2876}, orcid-numbers = {Herczeg, Róbert/0000-0002-5903-0082} }