TY - JOUR AU - Balogh, Lili AU - Olah, Katalin AU - Santa, Soma AU - Majerhoffer, Nora AU - Németh, Tamás TI - Novel and potential future therapeutic options in systemic autoimmune diseases JF - FRONTIERS IN IMMUNOLOGY J2 - FRONT IMMUNOL VL - 15 PY - 2024 PG - 16 SN - 1664-3224 DO - 10.3389/fimmu.2024.1249500 UR - https://m2.mtmt.hu/api/publication/34775042 ID - 34775042 N1 - Department of Physiology, Semmelweis University School of Medicine, Budapest, Hungary MTA-SE “Lendület” Translational Rheumatology Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary Department of Rheumatology and Clinical Immunology, Semmelweis University, Budapest, Hungary Department of Internal Medicine and Oncology, Semmelweis University, Budapest, Hungary Export Date: 11 April 2024 Correspondence Address: Németh, T.; Department of Physiology, Hungary; email: nemeth.tamas@med.semmelweis-univ.hu AB - Autoimmune inflammation is caused by the loss of tolerance to specific self-antigens and can result in organ-specific or systemic disorders. Systemic autoimmune diseases affect a significant portion of the population with an increasing rate of incidence, which means that is essential to have effective therapies to control these chronic disorders. Unfortunately, several patients with systemic autoimmune diseases do not respond at all or just partially respond to available conventional synthetic disease-modifying antirheumatic drugs and targeted therapies. However, during the past few years, some new medications have been approved and can be used in real-life clinical settings. Meanwhile, several new candidates appeared and can offer promising novel treatment options in the future. Here, we summarize the newly available medications and the most encouraging drug candidates in the treatment of systemic lupus erythematosus, rheumatoid arthritis, Sjogren's disease, systemic sclerosis, systemic vasculitis, and autoimmune myositis. LA - English DB - MTMT ER - TY - JOUR AU - Káposztás, Eszter Gertrúd AU - Balogh, Lili AU - Mócsai, Attila AU - Kemecsei, Éva AU - Jakus, Zoltán AU - Németh, Tamás TI - The selective inhibition of the Syk tyrosine kinase ameliorates experimental autoimmune arthritis JF - FRONTIERS IN IMMUNOLOGY J2 - FRONT IMMUNOL VL - 14 PY - 2023 PG - 12 SN - 1664-3224 DO - 10.3389/fimmu.2023.1279155 UR - https://m2.mtmt.hu/api/publication/34424360 ID - 34424360 AB - Autoimmune arthritis – such as rheumatoid arthritis – affect a significant proportion of the population, which can cause everyday joint pain, decreased mobility and reduced quality of life. Despite having more and more therapeutic options available, there are still a lot of patients who cannot reach remission or low disease activity by current therapies. This causes an urgent need for the development of new treatment options. The Syk tyrosine kinase plays an essential role in B cell receptor, Fc receptor and integrin signaling. It has been shown that the hematopoietic cell-specific deletion of Syk resulted in a complete protection against autoantibody-induced experimental arthritis. This prompted us to test the effect of entospletinib, a second generation, Syk-selective inhibitor, which has a tolerable safety profile according to hematological clinical trials, in experimental autoimmune arthritis. We found that entospletinib dose-dependently decreased the macroscopic signs of joint inflammation, while it did not affect the health status of the animals. In line with these findings, local neutrophil accumulation and cytokine levels were reduced compared to the vehicle-treated group, while macrophage accumulation and synovial fibroblast numbers were not significantly altered. Meanwhile, entospletinib dose-dependently decreased the cell responses of immune complex- or integrin ligand-activated neutrophils. Overall, we found that selective Syk inhibition by entospletinib reduced the activity of autoantibody-induced experimental arthritis, which seems to be based mainly on the effect of the inhibitor on neutrophil functions. Our data raise the possibility that entospletinib could be a good drug candidate in the treatment of human autoimmune arthritis. LA - English DB - MTMT ER - TY - JOUR AU - Futosi, Krisztina AU - Németh, Tamás AU - Horváth, Ádám István AU - Abram, Clare L AU - Tusnády, Simon AU - Lowell, Clifford A AU - Helyes, Zsuzsanna AU - Mócsai, Attila TI - Myeloid Src-family kinases are critical for neutrophil-mediated autoinflammation in gout and motheaten models. JF - JOURNAL OF EXPERIMENTAL MEDICINE J2 - J EXP MED VL - 220 PY - 2023 IS - 7 SN - 0022-1007 DO - 10.1084/jem.20221010 UR - https://m2.mtmt.hu/api/publication/33770181 ID - 33770181 N1 - Funding Agency and Grant Number: Hungarian Ministry of National Economy [VEKOP-2.3.2-16-2016-00002]; Hungarian National Research, Development and Innovation Fund [KKP-129954, TKP2021-EGA-24, FK132251, TKP2021-EGA-29, K-138046, TKP2021-EGA-16]; European Social Fund; European Union H2020 IMI2 program (RTCure project) [UNKP-20-5-SE-4]; Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences; New National Excellence Program of the Ministry for Innovation and Technology [UNKP-21-5-SE-2, 2017-1.2.1-NKP-2017-00002]; National Brain Research Program [EFOP-3.6.1.-16-2016-00004]; Hungarian National Academy of Scientist Education; [777357] Funding text: This work was supported by the Hungarian Ministry of National Economy (VEKOP-2.3.2-16-2016-00002 to A. Mocsai), the Hungarian National Research, Development and Innovation Fund (KKP-129954 and TKP2021-EGA-24 to A. Mocsai, FK132251 and TKP2021-EGA-29 to T. Nemeth, K-138046 and TKP2021-EGA-16 to Z. Helyes), the European Social Fund (EFOP-3.6.1.-16-2016-00004), the European Union H2020 IMI2 program (RTCure project No. 777357), the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences (to K. Futosi and T. Nemeth), the New National Excellence Program of the Ministry for Innovation and Technology (UNKP-20-5-SE-4 and UNKP-21-5-SE-2 to T. Nemeth), and the National Brain Research Program (2017-1.2.1-NKP-2017-00002 to Z. Helyes). S. Tusnady was supported by the Hungarian National Academy of Scientist Education. AB - Autoinflammatory diseases include a number of monogenic systemic inflammatory diseases, as well as acquired autoinflammatory diseases such as gout. Here, we show that the myeloid Src-family kinases Hck, Fgr, and Lyn are critical for experimental models of gout, as well as for genetically determined systemic inflammation in the Ptpn6me-v/me-v (motheaten viable) mouse model. The Hck-/-Fgr-/-Lyn-/- mutation abrogated various monosodium urate (MSU) crystal-induced pro-inflammatory responses of neutrophils, and protected mice from the development of gouty arthritis. The Src-family inhibitor dasatinib abrogated MSU crystal-induced responses of human neutrophils and reduced experimental gouty arthritis in mice. The Hck-/-Fgr-/-Lyn-/- mutation also abrogated spontaneous inflammation and prolonged the survival of the Ptpn6me-v/me-v mice. Spontaneous adhesion and superoxide release of Ptpn6me-v/me-v neutrophils were also abolished by the Hck-/-Fgr-/-Lyn-/- mutation. Excessive activation of tyrosine phosphorylation pathways in myeloid cells may characterize a subset of autoinflammatory diseases. LA - English DB - MTMT ER - TY - JOUR AU - Németh, Tamás AU - Balogh, Lili AU - Káposztás, Eszter Gertrúd AU - Szilveszter, Kata AU - Mócsai, Attila TI - Neutrophil-specific Syk expression is crucial for skin disease in experimental epidermolysis bullosa acquisita JF - JOURNAL OF INVESTIGATIVE DERMATOLOGY J2 - J INVEST DERMATOL VL - 143 PY - 2023 IS - 7 SP - 1147 EP - 1156 PG - 10 SN - 0022-202X DO - 10.1016/j.jid.2022.12.016 UR - https://m2.mtmt.hu/api/publication/33623361 ID - 33623361 LA - English DB - MTMT ER - TY - JOUR AU - Németh, Tamás AU - Nagy, György AU - Pap, Thomas TI - Synovial fibroblasts as potential drug targets in rheumatoid arthritis, where do we stand and where shall we go? JF - ANNALS OF THE RHEUMATIC DISEASES J2 - ANN RHEUM DIS VL - 81 PY - 2022 SP - 1055 EP - 1064 PG - 10 SN - 0003-4967 DO - 10.1136/annrheumdis-2021-222021 UR - https://m2.mtmt.hu/api/publication/32923734 ID - 32923734 N1 - Funding Agency and Grant Number: Hungarian National Research, Development and Innovation Office [FK 132251, K 131479, TKP2021-EGA-29]; European Union's H2020 IMI2 program (RTCure project) [777357]; Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences; New National Excellence Program of the Ministry for Innovation and Technology from the National Research, Development and Innovation Fund [UNKP 20-5-SE-4, UNKP-21-5-SE-2] Funding text: This work was funded and supported by the Hungarian National Research, Development and Innovation Office (No. FK 132251 to TN, No. K 131479 to GN and No. TKP2021-EGA-29 to TN and GN), the European Union's H2020 IMI2 program (RTCure project; No. 777357), the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences (to TN) and the New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund (No. UNKP 20-5-SE-4 and UNKP-21-5-SE-2 to TN). AB - Fibroblast-like synoviocytes or synovial fibroblasts (FLS) are important cellular components of the inner layer of the joint capsule, referred to as the synovial membrane. They can be found in both layers of this synovial membrane and contribute to normal joint function by producing extracellular matrix components and lubricants. However, under inflammatory conditions like in rheumatoid arthritis (RA), they may start to proliferate, undergo phenotypical changes and become central elements in the perpetuation of inflammation through their direct and indirect destructive functions. Their importance in autoimmune joint disorders makes them attractive cellular targets, and as mesenchymal-derived cells, their inhibition may be carried out without immunosuppressive consequences. Here, we aim to give an overview of our current understanding of the target potential of these cells in RA. LA - English DB - MTMT ER - TY - JOUR AU - Zajta, Erik AU - Csonka, Katalin AU - Tóth, Adél AU - Tiszlavicz, László AU - Németh, Tamás AU - Orosz, Anita AU - Novák, Ádám AU - Csikós, Máté Lajos AU - Vágvölgyi, Csaba AU - Mócsai, Attila AU - Gácser, Attila TI - Signaling through Syk or CARD9 Mediates Species-Specific Anti-Candida Protection in Bone Marrow Chimeric Mice JF - MBIO J2 - MBIO VL - 12 PY - 2021 IS - 4 PG - 18 SN - 2161-2129 DO - 10.1128/mBio.01608-21 UR - https://m2.mtmt.hu/api/publication/32169581 ID - 32169581 N1 - HCEMM-USZ Fungal Pathogens Research Group, Department of Microbiology, Faculty of Science and Informatics, University of Szeged, Szeged, Hungary Department of Pathology, University of Szeged, Szeged, Hungary Department of Physiology, Semmelweis University School of Medicine, Budapest, Hungary MTA-SZTE “Lendület” Mycobiome Research Group, University of Szeged, Szeged, Hungary Department of Rheumatology and Clinical Immunology, Semmelweis University, Budapest, Hungary Export Date: 14 September 2021 Correspondence Address: Gácser, A.; HCEMM-USZ Fungal Pathogens Research Group, Hungary; email: gacsera@bio.u-szeged.hu Funding details: 739593 Funding details: VEKOP-2.3.2-16-2016-00002 Funding details: FK 132251, KKP129954 Funding details: Magyar Tudományos Akadémia, MTA, BO/ 00520/20/5 Funding details: Nemzeti Kutatási Fejlesztési és Innovációs Hivatal, NKFIH, -15-2016-00035, GINOP-2.3.2, K 123952, LP2018-15/2018 Funding details: Nemzeti Kutatási, Fejlesztési és Innovaciós Alap, NKFIA, UNKP 20-5-SE-4 Funding details: Innovációs és Technológiai Minisztérium Funding text 1: A.G. was supported by grants 20391 3/2018/FEKUSTRAT, NKFIH K 123952, and GINOP-2.3.2.-15-2016-00035. A.G., E.Z., K.Cs., and Á.N. were additionally funded by LP2018-15/2018. This work was funded and supported by the Hungarian National Research, Development and Innovation Office (NKFIH-OTKA grant no. KKP129954 to A.M. and NKFIH-OTKA grant no. FK 132251 to T.N.), the Hungarian Ministry of National Economy VEKOP-2.3.2-16-2016-00002 (to A.M.), the János Bolyai Research Scholarship of the Hungarian Academy of Sciences (no. BO/ 00520/20/5 to T.N.), and the New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund (No. UNKP 20-5-SE-4 to T.N.). The project received funding from the EU's Horizon 2020 research and innovation program under grant agreement no. 739593. HCEMM-USZ Fungal Pathogens Research Group, Department of Microbiology, Faculty of Science and Informatics, University of Szeged, Szeged, Hungary Department of Pathology, University of Szeged, Szeged, Hungary Department of Physiology, Semmelweis University School of Medicine, Budapest, Hungary MTA-SZTE “Lendület” Mycobiome Research Group, University of Szeged, Szeged, Hungary Department of Rheumatology and Clinical Immunology, Semmelweis University, Budapest, Hungary Export Date: 16 September 2021 Correspondence Address: Gácser, A.; HCEMM-USZ Fungal Pathogens Research Group, Hungary; email: gacsera@bio.u-szeged.hu Funding details: 739593 Funding details: VEKOP-2.3.2-16-2016-00002 Funding details: FK 132251, KKP129954 Funding details: Magyar Tudományos Akadémia, MTA, BO/ 00520/20/5 Funding details: Nemzeti Kutatási Fejlesztési és Innovációs Hivatal, NKFIH, -15-2016-00035, GINOP-2.3.2, K 123952, LP2018-15/2018 Funding details: Nemzeti Kutatási, Fejlesztési és Innovaciós Alap, NKFIA, UNKP 20-5-SE-4 Funding details: Innovációs és Technológiai Minisztérium Funding text 1: A.G. was supported by grants 20391 3/2018/FEKUSTRAT, NKFIH K 123952, and GINOP-2.3.2.-15-2016-00035. A.G., E.Z., K.Cs., and Á.N. were additionally funded by LP2018-15/2018. This work was funded and supported by the Hungarian National Research, Development and Innovation Office (NKFIH-OTKA grant no. KKP129954 to A.M. and NKFIH-OTKA grant no. FK 132251 to T.N.), the Hungarian Ministry of National Economy VEKOP-2.3.2-16-2016-00002 (to A.M.), the János Bolyai Research Scholarship of the Hungarian Academy of Sciences (no. BO/ 00520/20/5 to T.N.), and the New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund (No. UNKP 20-5-SE-4 to T.N.). The project received funding from the EU's Horizon 2020 research and innovation program under grant agreement no. 739593. LA - English DB - MTMT ER - TY - JOUR AU - Németh, Tamás AU - Sperandio, M. AU - Mócsai, Attila TI - Neutrophils as emerging therapeutic targets JF - NATURE REVIEWS DRUG DISCOVERY J2 - NAT REV DRUG DISCOV VL - 19 PY - 2020 IS - 4 SP - 253 EP - 275 PG - 23 SN - 1474-1776 DO - 10.1038/s41573-019-0054-z UR - https://m2.mtmt.hu/api/publication/31156872 ID - 31156872 AB - Neutrophils are the most abundant circulating leukocytes, being the first line of defence against bacterial and fungal infections. However, neutrophils also contribute to tissue damage during various autoimmune and inflammatory diseases, and play important roles in cancer progression. The intimate but complex involvement of neutrophils in various diseases makes them exciting targets for therapeutic intervention but also necessitates differentiation of beneficial responses from potentially detrimental side effects. A variety of approaches to therapeutically target neutrophils have emerged, including strategies to enhance, inhibit or restore neutrophil function, with several agents entering clinical trials. However, challenges and controversies in the field remain. © 2020, Springer Nature Limited. LA - English DB - MTMT ER - TY - JOUR AU - Németh, Tamás AU - Szilveszter, Kata AU - Sitaru, Cassian AU - Mócsai, Attila TI - Neutrophil-specific deletion of the Syk tyrosine kinase abrogates the development of experimental epidermolysis bullosa acquisita JF - EUROPEAN JOURNAL OF CLINICAL INVESTIGATION J2 - EUR J CLIN INVEST VL - 49 PY - 2019 IS - Suppl. 1 SP - 139 EP - 139 PG - 1 SN - 0014-2972 UR - https://m2.mtmt.hu/api/publication/31900984 ID - 31900984 LA - English DB - MTMT ER - TY - JOUR AU - Szilveszter, Kata AU - Németh, Tamás AU - Mócsai, Attila TI - Investigating the role of PLC gamma 2 in autoimmune skin inflammation JF - EUROPEAN JOURNAL OF CLINICAL INVESTIGATION J2 - EUR J CLIN INVEST VL - 49 PY - 2019 IS - Suppl. 1 SP - 135 EP - 135 PG - 1 SN - 0014-2972 DO - 10.1111/eci.13110 UR - https://m2.mtmt.hu/api/publication/31900972 ID - 31900972 LA - English DB - MTMT ER - TY - JOUR AU - Szilveszter, Kata AU - Németh, Tamás AU - Mócsai, Attila TI - Characterizing the Role of PLC gamma 2 in Autoantibody-induced Skin Inflammation JF - JOURNAL OF INVESTIGATIVE DERMATOLOGY J2 - J INVEST DERMATOL VL - 139 PY - 2019 IS - 9 Suppl. S SP - S279 EP - S279 SN - 0022-202X DO - 10.1016/j.jid.2019.07.381 UR - https://m2.mtmt.hu/api/publication/31900946 ID - 31900946 LA - English DB - MTMT ER -