Ivana Munitic

Ivana Munitic
University of Rijeka · Department of Biotechnology

27.12
 · 
MD, PhD

About

26
Publications
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602
Citations

Publications

Publications (26)
Article
Full-text available
Despite wide genetic, environmental and clinical heterogeneity in amyotrophic lateral sclerosis, a rapidly fatal neurodegenerative disease targeting motoneurons, neuroinflammation is a common finding. It is marked by local glial activation, T cell infiltration and systemic immune system activation. The immune system has a prominent role in the path...
Article
Full-text available
The toolkit for repairing damaged neurons in amyotrophic lateral sclerosis (ALS) and spinal cord injury (SCI) is extremely limited. Here, we reviewed the in vitro and in vivo studies and clinical trials on nonneuronal cells in the neurodegenerative processes common to both these conditions. Special focus was directed to microglia and astrocytes, be...
Article
Full-text available
ALS is the most frequent motor neuron disorder in adults with suggested complex relationship regarding gender. Studies investigating ALS and hormones have provided varying results. ALS onset during pregnancy is uncommon and pregnancy after the ALS symptom onset is even rarer. We present three patients with the onset of ALS symptoms before or during...
Preprint
Full-text available
Amyotrophic lateral sclerosis (ALS) is a rapidly progressive fatal neurodegenerative disease affecting 1 in 350 people. The aim of Project MinE is to elucidate the pathophysiology of ALS through whole-genome sequencing at least 15,000 ALS patients and 7,500 controls at 30X coverage. Here, we present the Project MinE data browser (databrowser.projec...
Article
Full-text available
Mutations in a ubiquitin (Ub)-binding adaptor protein optineurin have been found in amyotrophic lateral sclerosis (ALS), a neurodegenerative disease with a prominent neuroinflammatory component. Unlike more frequent ALS mutations which cause disease by gaining toxic properties such as aggregation, mutated optineurin is thought to cause disease by l...
Article
Full-text available
When optineurin mutations showed up on the amyotrophic lateral sclerosis (ALS) landscape in 2010, they differed from most other ALS-causing genes. They seemed to act by loss- rather than gain-of-function, and it was unclear how a polyubiquitin-binding adaptor protein, which was proposed to regulate a variety of cellular functions including cell sig...
Article
Full-text available
Photodynamic therapy (PDT) combines a photosensitiser, light and molecular oxygen to induce oxidative stress that can be used to kill pathogens, cancer cells and other highly proliferative cells. There is a growing number of clinically approved photosensitisers and applications of PDT, whose main advantages include the possibility of selective targ...
Article
Full-text available
Background After viral infection and the stimulation of some pattern-recognition receptors, TANK-binding kinase I (TBK1) is activated by K63-linked polyubiquitination followed by trans-autophosphorylation. While the activated TBK1 induces type I interferon production by phosphorylating the transcription factor IRF3, the precise molecular mechanisms...
Article
Full-text available
Pathogen-associated molecular pattern (PAMP) recognition leads to TANK-binding kinase (TBK1) polyubiquitination and activation by trans-autophosphorylation, resulting in IFN-β production. Here we describe a mouse model of optineurin insufficiency (OptnΔ(157) ) in which the TBK1-interacting N-terminus of optineurin was deleted. PAMP-stimulated cells...
Article
Full-text available
Author Summary Sepsis refers to life-threatening systemic inflammation, often caused by infection with bacteria that produce lipopolysaccharide (LPS). Glucocorticoids, immunosuppressive hormones produced by the adrenals, have been used to treat sepsis for over 50 y, but little is known about the role of endogenous (naturally occurring) glucocortico...
Article
Full-text available
Cellular inhibitor of apoptosis proteins (c-IAP) 1 and 2 are widely expressed ubiquitin protein ligases that regulate a variety of cellular functions, including the sensitivity of T cells to co-stimulation. 4-1BB is a TNFR family member that signals via a complex that includes TRAF family members and the c-IAPs to upregulate NF-κB and ERK, and has...
Article
Full-text available
Optineurin is a widely expressed polyubiquitin-binding protein that has been implicated in regulating cell signaling via its NF-κB essential modulator-homologous C-terminal ubiquitin (Ub)-binding region. Its functions are controversial, with in vitro studies finding that optineurin suppressed TNF-mediated NF-κB activation and virus-induced activati...
Article
Full-text available
Engagement of the receptor CD27 by CD70 affects the magnitude and quality of T cell responses in a variety of infection models, and exaggerated signaling via this pathway results in enhanced immune responses and autoimmunity. One means by which signaling is regulated is tight control of cell surface CD70, which is expressed on dendritic cells (DCs)...
Article
Full-text available
CD27 interactions with its ligand, CD70, are thought to be necessary for optimal primary and memory adaptive immune responses to a variety of pathogens. Thus far, all studies addressing the function of the CD27-CD70 axis have been performed in mice lacking CD27, in those overexpressing CD70, or in those in which these molecules were blocked or mimi...
Article
Full-text available
An efficient immune response requires coordination between innate and adaptive immunity, which act through cells different in origin and function. Here we report the identification of thymus-derived αβ-T-cell receptor(+) cells that express CD11c and major histocompatibility complex class II, and require FLT3 ligand for development (T(DC)). T(DC) ex...
Article
Full-text available
Several cytokines (including IL-2, IL-7, IL-15, and IL-21) that signal through receptors sharing the common gamma chain (gamma(c)) are critical for the generation and peripheral homeostasis of naive and memory T cells. Recently, we demonstrated that effector functions fail to develop in CD4(+) T cells that differentiate in the absence of gamma(c)....
Article
Naïve CD8 T cells differentiate in response to antigen stimulation. They acquire the capacity to express multiple effector molecules and mediate effector functions that contribute to infection control. Once antigen loads are reduced they revert progressively to a less activated status and eventually reach a steady-state referred to as "memory" that...
Article
Full-text available
To evaluate the impact of immunodominance on CD8 T-cell properties, we compared the functional properties of dominant and subdominant populations in the response to lymphocytic choriomeningitis virus (LCMV). To improve functional discrimination, in addition to the usual tests of phenotype and function, we used a sensitive technique that allows the...
Article
The ability of the adaptive immune system to respond rapidly and robustly upon repeated antigen exposure is known as immunologic memory, and it is thought that acquisition of memory T-cell function is an irreversible differentiation event. In this study, we report that many phenotypic and functional characteristics of antigen-specific CD8 memory T...
Article
Full-text available
To study in vivo CD8 T cell differentiation, we quantified the coexpression of multiple genes in single cells throughout immune responses. After in vitro activation, CD8 T cells rapidly express effector molecules and cease their expression when the antigen is removed. Gene behavior after in vivo activation, in contrast, was quite heterogeneous. Dif...
Article
Full-text available
The commitment of naive T cells to proliferate is a function of the strength and duration of stimuli mediated by the TCR and coreceptors. Ranges of 2-20 h of stimulation have been reported as necessary in vitro. Whether T cells actually experience uninterrupted stimulation for such long periods under physiological conditions is controversial. Here...
Article
Full-text available
Interleukin-7 receptor (IL-7R) levels are tightly controlled during ontogeny: high on double-negative (DN) cells, absent on double-positive (DP) cells, and high once again on thymocytes undergoing positive selection. To determine if loss of IL-7-mediated survival signals in DP cells is necessary for normal antigen-specific selection, we created T-l...
Article
Full-text available
The ability of a T cell to be activated is critically regulated by the number of TCRs expressed on the plasma membrane. Cell surface TCR expression is influenced by dynamic processes such as synthesis and transport of newly assembled receptors, endocytosis of surface TCR, and recycling to the plasma membrane of internalized receptors. In this study...

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