Tamás Németh

• MD, PhD
• Lecturer at Semmelweis University

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 ther...

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 (mothe...

Autoantibodies against the dermal-epidermal junction component type VII collagen (C7) trigger skin disease in the inflammatory form of epidermolysis bullosa acquisita. We have previously identified the Syk tyrosine kinase as a crucial participant of anti-C7 antibody-induced experimental epidermolysis bullosa acquisita. However, it is still unclear...

While C. albicans remains the most clinically significant Candida species, C. parapsilosis is an emerging pathogen with increased affinity to neonates. Syk/CARD9 signaling is crucial in immunity to C. albicans , but its role in in vivo responses to other pathogenic Candida species is largely unexplored.

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 d...

Tyrosine kinases relay signals from diverse leukocyte antigen receptors, innate immune receptors, and cytokine receptors, and therefore mediate the recruitment and activation of various leukocyte populations. Non-receptor tyrosine kinases of the Jak, Src, Syk, and Btk families play major roles in various immune-mediated disorders, and small-molecul...

Activating Fcγ receptors associated with Fc receptor γ-chain (FcRγ) are critical for mediating neutrophil effector functions in immune complex-mediated autoimmune diseases. FcRγ contains ITAM tyrosines and the in vivo role of these tyrosines has not been defined in neutrophils and arthritis. In this study, the in vivo functions of FcRγ ITAM tyrosin...

Mouse strains with specific deficiency of given hematopoietic lineages provide invaluable tools for understanding blood cell function in health and disease. Whereas neutrophils are dominant leukocytes in humans and mice, there are no widely useful genetic models of neutrophil deficiency in mice. In this study, we show that myeloid-specific deletion...

Autoantibody production and autoantibody-mediated inflammation are hallmarks of a number of autoimmune diseases. The K/BxN serum-transfer arthritis is one of the most widely used models of the effector phase of autoantibody-induced pathology. Several hematopoietic lineages including neutrophils, platelets, and mast cells have been proposed to contr...

The inflammatory form of epidermolysis bullosa acquisita is caused by autoantibodies against type VII collagen (C7), a component of the dermal-epidermal junction. We have previously shown that myeloid Src-family kinases mediate skin inflammation triggered by anti-C7 antibodies. Here we identify the Syk tyrosine kinase as a critical component of aut...

ARHGAP25 is a Rac-specific GTPase-activating protein that is expressed primarily in hematopoietic cells. The involvement of ARHGAP25 in regulating the recruitment of leukocytes to inflammatory sites was investigated in genetically modified mice. Using intravital microscopy, we show that Arhgap25 deficiency affects all steps of leukocyte recruitment...

During hematopoiesis, transcriptional programs are essential for the commitment and differentiation of progenitors into the different blood lineages. GATA1 is a transcription factor expressed in several hematopoietic lineages and essential for proper erythropoiesis and megakaryopoiesis. Megakaryocyte-specific genes, such as GP1BA, are known to be d...

As the first line of innate immune defense, neutrophils need to mount a rapid and robust antimicrobial response. Recent studies implicate various positive feedback amplification processes in achieving that goal. Feedback amplification ensures effective migration of neutrophils in shallow chemotactic gradients, multiple waves of neutrophil recruitme...

Neutrophils are terminally differentiated cells with limited transcriptional activity. The biological function of their gene expression changes is poorly understood. CARD9 regulates transcription during antifungal immunity but its role in sterile inflammation is unclear. Here we show that neutrophil CARD9 mediates pro-inflammatory chemokine/cytokin...

Neutrophils have traditionally been thought to play only a peripheral role in the genesis of many autoimmune and inflammatory diseases. However, recent studies in a variety of animal models suggest that these cells are central to the initiation and propagation of autoimmunity. The use of mouse models, which allow either deletion of neutrophils or t...

Emerging evidence suggests that the vascular endothelial growth factor receptor 2 (VEGFR2) and protein kinase D1 (PKD1) signaling axis plays a critical role in normal and pathological angiogenesis and inflammation related processes. Despite all efforts, the currently available therapeutic interventions are limited. Prior studies have also proved th...

Allergic contact dermatitis and its animal model, contact hypersensitivity (CHS), are T cell–mediated inflammatory skin diseases induced by contact allergens. Though numerous cellular and molecular players are known, the mechanism of chemical-induced sensitization remains poorly understood. Here, we identify neutrophils as crucial players in the se...

Objective Pituitary adenylate cyclase-activating polypeptide (PACAP) expressed in capsaicin-sensitive sensory neurons and immune cells has divergent functions in inflammatory and pain processes. This study was undertaken to investigate the involvement of PACAP in a mouse model of rheumatoid arthritis. Methods Arthritis was induced in PACAP(-/-) and...

Although Src family kinases participate in leukocyte function in vitro, such as integrin signal transduction, their role in inflammation in vivo is poorly understood. We show that Src family kinases play a critical role in myeloid cell-mediated in vivo inflammatory reactions. Mice lacking the Src family kinases Hck, Fgr, and Lyn in the hematopoieti...

Dasatinib is a tyrosine kinase inhibitor used to treat imatinib-resistant chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia. At present, little is known about how dasatinib influences nonmalignant cells. In the present study, we tested the effect of dasatinib on functional responses of normal mature human ne...

Though chronic autoimmune disorders such as rheumatoid arthritis or systemic lupus erythematosus affect a significant percentage of the human population and strongly diminish the quality of life and life expectancy in Western societies, the molecular pathomechanisms of those diseases are still poorly understood, hindering the development of novel t...

The purpose of this study was to explore how genetic deletion and pharmacological antagonism of the P2X7 receptor (P2rx7) alter mood-related behaviour, gene expression and stress reactivity in the brain. The forced swim test (FST), tail suspension test (TST) and amphetamine-induced hyperlocomotion (AH) tests were used in wild-type (P2rx7+/+) and P2...

Recent linkage studies associated a polymorphism in P2X7 receptor (P2X7R) gene with depressive disorders. The purpose of the study was to explore how genetic deletion and pharmacological antagonism of P2X7 receptors alter depressive behavior and related neurochemical parameters.

Beta(2) integrins of neutrophils play a critical role in innate immune defense, but they also participate in tissue destruction during autoimmune inflammation. p190RhoGAP (ArhGAP35), a regulator of Rho family small GTPases, is required for integrin signal transduction in fibroblasts. Prior studies have also suggested a role for p190RhoGAP in beta(2...

Immune complex-induced activation of neutrophils through cell surface FcRs plays a central role in the pathogenesis of autoimmune inflammatory diseases. These diseases are often modeled using genetically modified mice. However, in contrast to the number of studies on human cells, the identity of FcRs involved in immune complex activation of murine...

Immune complex-induced activation of neutrophils through cell surface FcRs plays a central role in the pathogenesis of autoimmune inflammatory diseases. These diseases are often modeled using genetically modified mice. However, in contrast to the number of studies on human cells, the identity of FcRs involved in immune complex activation of murine...