Nejvíce citovaný článek - PubMed ID 16990136
Antigen-presenting cells (APCs) are master regulators of the immune response by directly interacting with T cells to orchestrate distinct functional outcomes. Several types of professional APC exist, including conventional dendritic cells, B cells and macrophages, and numerous other cell types have non-classical roles in antigen presentation, such as thymic epithelial cells, endothelial cells and granulocytes. Accumulating evidence indicates the presence of a new family of APCs marked by the lineage-specifying transcription factor retinoic acid receptor-related orphan receptor-γt (RORγt) and demonstrates that these APCs have key roles in shaping immunity, inflammation and tolerance, particularly in the context of host-microorganism interactions. These RORγt+ APCs include subsets of group 3 innate lymphoid cells, extrathymic autoimmune regulator-expressing cells and, potentially, other emerging populations. Here, we summarize the major findings that led to the discovery of these RORγt+ APCs and their associated functions. We discuss discordance in recent reports and identify gaps in our knowledge in this burgeoning field, which has tremendous potential to advance our understanding of fundamental immune concepts.
- MeSH
- antigen prezentující buňky metabolismus MeSH
- endoteliální buňky MeSH
- jaderné receptory - podrodina 1, skupina F, člen 3 * metabolismus MeSH
- lidé MeSH
- lymfocyty * MeSH
- přirozená imunita MeSH
- transportní proteiny metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- jaderné receptory - podrodina 1, skupina F, člen 3 * MeSH
- transportní proteiny MeSH
Inflammatory bowel disease (IBD) is a lifelong inflammatory immune mediated disorder, encompassing Crohn's disease (CD) and ulcerative colitis (UC); however, the cause and specific pathogenesis of IBD is yet incompletely understood. Multiple cytokines produced by different immune cell types results in complex functional networks that constitute a highly regulated messaging network of signaling pathways. Applying biological mechanisms underlying IBD at the single omic level, technologies and genetic engineering enable the quantification of the pattern of released cytokines and new insights into the cytokine landscape of IBD. We focus on the existing literature dealing with the biology of pro- or anti-inflammatory cytokines and interactions that facilitate cell-based modulation of the immune system for IBD inflammation. We summarize the main roles of substantial cytokines in IBD related to homeostatic tissue functions and the remodeling of cytokine networks in IBD, which may be specifically valuable for successful cytokine-targeted therapies via marketed products. Cytokines and their receptors are validated targets for multiple therapeutic areas, we review the current strategies for therapeutic intervention and developing cytokine-targeted therapies. New biologics have shown efficacy in the last few decades for the management of IBD; unfortunately, many patients are nonresponsive or develop therapy resistance over time, creating a need for novel therapeutics. Thus, the treatment options for IBD beyond the immune-modifying anti-TNF agents or combination therapies are expanding rapidly. Further studies are needed to fully understand the immune response, networks of cytokines, and the direct pathogenetic relevance regarding individually tailored, safe and efficient targeted-biotherapeutics.
- Klíčová slova
- cytokines, inflammatory bowel disease, novel therapeutic targets,
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
INTRODUCTION: Alemtuzumab is highly effective in the treatment of patients with relapsing multiple sclerosis (PwRMS) and selectively targets the CD52 antigen, with a consequent profound lymphopenia, particularly of CD4+ T lymphocytes. However, the immunological basis of its long-term efficacy has not been clearly elucidated. METHODS: We followed up 29 alemtuzumab-treated RMS patients over a period of 72 months and studied the immunological reconstitution of their CD4+ T cell subsets by means of phenotypic and functional analysis and through mRNA-related molecule expression, comparing them to healthy subject (HS) values (rate 2:1). RESULTS: In patients receiving only two-course alemtuzumab, the percentage of CD4+ lymphocytes decreased and returned to basal levels only at month 48. Immune reconstitution of the CD4+ subsets was characterized by a significant increase (p < 0.001) in Treg cell percentage at month 24, when compared to baseline, and was accompanied by restoration of the Treg suppressor function that increased within a range from 2- to 6.5-fold compared to baseline and that persisted through to the end of the follow-up. Furthermore, a significant decrease in self-reactive myelin basic protein-specific Th17 (p < 0.0001) and Th1 (p < 0.05) cells reaching HS values was observed starting from month 12. There was a change in mRNA of cytokines, chemokines, and transcriptional factors related to Th17, Th1, and Treg cell subset changes, consequently suggesting a shift toward immunoregulation and a reduction of T cell recruitment to the central nervous system. CONCLUSIONS: These data provide further insight into the mechanism that could contribute to the long-term 6-year persistence of the clinical effect of alemtuzumab on RMS disease activity.
- Klíčová slova
- MBP (myelin basic protein), Treg cells, alemtuzumab, immune reconstitution, multiple sclerosis,
- MeSH
- alemtuzumab farmakologie terapeutické užití MeSH
- CD4-pozitivní T-lymfocyty MeSH
- lidé MeSH
- messenger RNA terapeutické užití MeSH
- následné studie MeSH
- roztroušená skleróza * farmakoterapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- alemtuzumab MeSH
- messenger RNA MeSH
Tick saliva is a rich source of pharmacologically and immunologically active molecules. These salivary components are indispensable for successful blood feeding on vertebrate hosts and are believed to facilitate the transmission of tick-borne pathogens. Here we present the functional and structural characterization of Iripin-3, a protein expressed in the salivary glands of the tick Ixodes ricinus, a European vector of tick-borne encephalitis and Lyme disease. Belonging to the serpin superfamily of protease inhibitors, Iripin-3 strongly inhibited the proteolytic activity of serine proteases kallikrein and matriptase. In an in vitro setup, Iripin-3 was capable of modulating the adaptive immune response as evidenced by reduced survival of mouse splenocytes, impaired proliferation of CD4+ T lymphocytes, suppression of the T helper type 1 immune response, and induction of regulatory T cell differentiation. Apart from altering acquired immunity, Iripin-3 also inhibited the extrinsic blood coagulation pathway and reduced the production of pro-inflammatory cytokine interleukin-6 by lipopolysaccharide-stimulated bone marrow-derived macrophages. In addition to its functional characterization, we present the crystal structure of cleaved Iripin-3 at 1.95 Å resolution. Iripin-3 proved to be a pluripotent salivary serpin with immunomodulatory and anti-hemostatic properties that could facilitate tick feeding via the suppression of host anti-tick defenses. Physiological relevance of Iripin-3 activities observed in vitro needs to be supported by appropriate in vivo experiments.
- Klíčová slova
- Ixodes ricinus, X-ray crystallography, adaptive immunity, blood coagulation, inflammation, saliva, serpin, tick,
- MeSH
- adaptivní imunita účinky léků MeSH
- aktivace lymfocytů účinky léků MeSH
- antikoagulancia izolace a purifikace farmakologie MeSH
- cytokiny metabolismus MeSH
- hemokoagulace účinky léků MeSH
- hmyzí proteiny izolace a purifikace farmakologie MeSH
- imunologické faktory izolace a purifikace farmakologie MeSH
- inhibitory proteas izolace a purifikace farmakologie MeSH
- klíště metabolismus MeSH
- králíci MeSH
- kultivované buňky MeSH
- lidé MeSH
- lymfocyty účinky léků imunologie metabolismus MeSH
- morčata MeSH
- myši inbrední C3H MeSH
- myši inbrední C57BL MeSH
- myši transgenní MeSH
- myši MeSH
- proliferace buněk účinky léků MeSH
- slezina účinky léků imunologie metabolismus MeSH
- slinné proteiny a peptidy izolace a purifikace farmakologie MeSH
- sliny metabolismus MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- lidé MeSH
- morčata MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antikoagulancia MeSH
- cytokiny MeSH
- hmyzí proteiny MeSH
- imunologické faktory MeSH
- inhibitory proteas MeSH
- slinné proteiny a peptidy MeSH
A balanced immune response is a cornerstone of healthy aging. Here, we uncover distinctive features of the long-lived blind mole-rat (Spalax spp.) adaptive immune system, relative to humans and mice. The T-cell repertoire remains diverse throughout the Spalax lifespan, suggesting a paucity of large long-lived clones of effector-memory T cells. Expression of master transcription factors of T-cell differentiation, as well as checkpoint and cytotoxicity genes, remains low as Spalax ages. The thymus shrinks as in mice and humans, while interleukin-7 and interleukin-7 receptor expression remains high, potentially reflecting the sustained homeostasis of naive T cells. With aging, immunoglobulin hypermutation level does not increase and the immunoglobulin-M repertoire remains diverse, suggesting shorter B-cell memory and sustained homeostasis of innate-like B cells. The Spalax adaptive immune system thus appears biased towards sustained functional and receptor diversity over specialized, long-lived effector-memory clones-a unique organizational strategy that potentially underlies this animal's extraordinary longevity and healthy aging.
- MeSH
- adaptivní imunita MeSH
- imunoglobuliny metabolismus MeSH
- interleukin-7 metabolismus MeSH
- lidé MeSH
- mikroftalmičtí podzemní hlodavci MeSH
- myši MeSH
- Spalax * genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- imunoglobuliny MeSH
- interleukin-7 MeSH
These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.
- MeSH
- DNA analýza MeSH
- falešně pozitivní reakce MeSH
- imunofenotypizace MeSH
- imunologické techniky * MeSH
- lidé MeSH
- proliferace buněk MeSH
- průtoková cytometrie MeSH
- řízení kvality MeSH
- RNA analýza MeSH
- separace buněk MeSH
- směrnice jako téma * MeSH
- software MeSH
- T-lymfocyty cytologie MeSH
- výzkumný projekt MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Názvy látek
- DNA MeSH
- RNA MeSH
Inflammatory or anti-inflammatory? That is the question as far as the acute-phase response and its mediators, the pentraxins, are concerned. Only some ten years ago, the classical or short pentraxin C-reactive protein and the newly discovered long pentraxin PTX3 were considered to exert most of the detrimental effects of acute inflammation, whether microbial or sterile in origin. However, accumulating evidence suggests an at least dichotomous, context-dependent outcome attributable to the pentraxins, if not a straightforward anti-inflammatory nature of the acute-phase response. This paper is focused on the inherent effects of pentraxin 3 in inflammatory responses, mainly in coronary artery disease and in Aspergillus fumigatus infection. Both are examples of inflammatory reactions in which PTX3 is substantially involved; the former sterile, the latter infectious in origin. Apart from different inducing noxae, similarities in the pathogenesis of the two are striking. All the same, the introductory question still persists: is the ultimate impact of PTX3 in these conditions inflammatory or anti-inflammatory, paradoxical as the latter might appear? We try to provide an answer such as it emerges in the light of recent findings.
- MeSH
- Aspergillus fumigatus metabolismus MeSH
- ateroskleróza metabolismus MeSH
- C-reaktivní protein genetika fyziologie MeSH
- infarkt myokardu metabolismus MeSH
- kardiovaskulární nemoci krev metabolismus MeSH
- komplement MeSH
- lidé MeSH
- myši MeSH
- neutrofily metabolismus MeSH
- přirozená imunita MeSH
- reperfuzní poškození MeSH
- sérový amyloidový protein genetika fyziologie MeSH
- zánět MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- C-reaktivní protein MeSH
- komplement MeSH
- PTX3 protein MeSH Prohlížeč
- sérový amyloidový protein MeSH
Hyper-immunoglobulin (Ig)E syndrome (HIES) is a primary immunodeficiency associated with mutations in STAT3 resulting in impaired development of T helper type 17 (Th17) lymphocytes. HIES patients with a reduced frequency of Th17 cells present with infections caused by Staphylococcus aureus and/or Candida strains. The same spectrum of pathogens is present in patients with chronic granulomatous disease (CGD).We analysed the characteristics of the Th17 compartment in HIES and CGD. HIES patients showed very low numbers of Th17 cells. By contrast, the frequency of Th17 cells and production of Th17-derived cytokines was significantly higher among CGD patients when compared to both control samples and HIES. Naive CD4(+) cells in CGD patients had a normal capacity to differentiate into IL-17-producing cells and the numbers of Th17 cells in the CGD patients normalized following successful bone marrow transplantation. Our findings complement recent data on the importance of Th17 cells for elimination of infections with C. albicans and S. aureus.
- MeSH
- buněčná diferenciace imunologie MeSH
- buňky Th17 imunologie metabolismus patologie MeSH
- Candida albicans růst a vývoj MeSH
- chronická granulomatózní nemoc genetika imunologie metabolismus patologie terapie MeSH
- dítě MeSH
- dospělí MeSH
- ELISA MeSH
- homologní transplantace MeSH
- interferon gama imunologie metabolismus MeSH
- interleukin-17 imunologie metabolismus MeSH
- Jobův syndrom genetika imunologie metabolismus patologie MeSH
- kandidóza imunologie mikrobiologie MeSH
- lidé MeSH
- membránové glykoproteiny genetika imunologie metabolismus MeSH
- mutace MeSH
- NADPH-oxidasa 2 MeSH
- NADPH-oxidasy genetika imunologie metabolismus MeSH
- počet lymfocytů MeSH
- předškolní dítě MeSH
- průtoková cytometrie MeSH
- stafylokokové infekce imunologie mikrobiologie MeSH
- Staphylococcus aureus růst a vývoj MeSH
- studie případů a kontrol MeSH
- transkripční faktor STAT3 genetika imunologie metabolismus MeSH
- transplantace hematopoetických kmenových buněk MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- CYBB protein, human MeSH Prohlížeč
- interferon gama MeSH
- interleukin-17 MeSH
- membránové glykoproteiny MeSH
- NADPH-oxidasa 2 MeSH
- NADPH-oxidasy MeSH
- transkripční faktor STAT3 MeSH
