Roztroušená skleróza je závažné autoimunitní onemocnění centrální nervové soustavy. Vyskytuje se s relativně vysokou prevalencí, a to především u mladých lidí. K vývoji nových léčiv je zásadní pochopení patogeneze tohoto onemocnění. Té se účastní všechny složky imunity. Zkoumány jsou především lymfocytární populace. Dříve se za hlavní příčinu roztroušené sklerózy považovala nerovnováha mezi subtypy helperských lymfocytů Th1 a Th2. V posledních letech byl ale prokázán vliv dalších buněčných elementů, jako jsou B lymfocyty, cytotoxické T lymfocyty, a byly objeveny i nové buněčné typy, regulační T lymfocyty a helperské Th17. Tento článek má za cíl přiblížit základní role jednotlivých lymfocytárních podtypů v rozvoji roztroušené sklerózy, a to se zaměřením především na regulační T lymfocyty a pomocné Th17.

Multiple sclerosis is a serious autoimmune disease of the central nervous system. It occurs with relatively high prevalence, especially in young people. It is essential to understand the pathogenesis of this disease in order to develop new treatments. All components of immunity are involved in this process but current research mainly focuses on lymphocyte populations. Previously, imbalance between subtypes of helper lymphocytes Th1 and Th2 was considered as the main cause of multiple sclerosis. Recently, the influence of other cell elements, such as B lymphocytes, cytotoxic T lymphocytes, was shown. Moreover, new cell types, regulatory T lymphocytes and helper Th17 lymphocytes, have been discovered. The aim of this article is to describe the main roles of individual lymphocyte subtypes in multiple sclerosis pathogenesis, focusing first on regulatory T lymphocytes and helper Th17 lymphocytes.

• MeSH
• adaptivní imunita * fyziologie   MeSH
• B-lymfocyty fyziologie   MeSH
• buňky Th17 fyziologie   patologie   MeSH
• lidé MeSH
• regulační T-lymfocyty fyziologie   patologie   MeSH
• roztroušená skleróza * etiologie   MeSH
• T-lymfocyty fyziologie   klasifikace   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

Regulatory T (Treg) cells prevent autoimmunity by limiting immune responses and inflammation in the secondary lymphoid organs and nonlymphoid tissues. While unique subsets of Treg cells have been described in some nonlymphoid tissues, their relationship to Treg cells in secondary lymphoid organs and circulation remains unclear. Furthermore, it is possible that Treg cells from similar tissue types share largely similar properties. We have identified a short-lived effector Treg cell subset that expresses the α2 integrin, CD49b, and exhibits a unique tissue distribution, being abundant in peripheral blood, vasculature, skin, and skin-draining lymph nodes, but uncommon in the intestines and in viscera-draining lymph nodes. CD49b+ Treg cells, which display superior functionality revealed by in vitro and in vivo assays, appear to develop after multiple rounds of cell division and TCR-dependent activation. Accordingly, single-cell RNA-seq analysis placed these cells at the apex of the Treg developmental trajectory. These results shed light on the identity and development of a functionally potent subset of mature effector Treg cells that recirculate through and survey peripheral tissues.

• MeSH
• cévy imunologie   MeSH
• imunitní dozor * MeSH
• integrin alfa2 genetika   imunologie   MeSH
• kůže krevní zásobení   cytologie   imunologie   MeSH
• lymfatické uzliny krevní zásobení   cytologie   imunologie   MeSH
• myši transgenní MeSH
• myši MeSH
• regulační T-lymfocyty cytologie   imunologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

Regulatory T cells (Tregs) are a specialized subpopulation of T cells that act to suppress immune response, thereby maintaining homeostasis and self-tolerance. It has been shown that Tregs are able to inhibit T cell proliferation and cytokine production and play a critical role in preventing autoimmunity. Different subsets with various functions of Treg cells exist. Tregs can be usually identified by flow cytometry. The most specific marker for these cells is FoxP3, which is localized intracellulary. Selected surface markers such as CD25high (high molecular density) and CD127low (low molecular density) could serve as surrogate markers to detect Tregs in a routine clinical practice. Dysregulation in Treg cell frequency or functions may lead to the development of autoimmune disease. Therapeutical Treg modulation is considered to be a promising therapeutical approach to treat some selected disorders, such as allergies, and to prevent allograft rejection.

• Klíčová slova
• Regulatory T cells, Immunopathology, Regulation,
• MeSH
• autoimunitní nemoci imunologie   MeSH
• autotolerance imunologie   MeSH
• CD4-pozitivní T-lymfocyty imunologie   MeSH
• financování organizované MeSH
• nemoci imunitního systému imunologie   MeSH
• podskupiny lymfocytů MeSH
• průtoková cytometrie MeSH
• regulační T-lymfocyty imunologie   MeSH
• Publikační typ
• přehledy MeSH

IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide. Current studies have shown that the Th17/Treg immune balance may be involved in the occurrence of IgAN, but the exact mechanism is still unclear. Indoleamine 2,3-dioxygenase (IDO) is an enzyme that catalyses degradation of tryptophan (Trp) through the kynurenine (Kyn) pathway; it can control inflammation and immune response by inducing Trp starvation. IDO may be a key molecule in regulating the Th17/Treg immune balance. However, it is not clear whether IDO is involved in the IgAN disease occurrence by regulating the Th17/Treg immune balance. In this study, an IgAN mouse model was established. The mice were intraperitoneally inoculated with IDO inhibitor 1-MT or agonist ISS-ODN to observe whether the IDO signalling pathway participates in the occurrence and development of IgAN by regulating the Th17/Treg immune balance. The results showed that IDO inhibitor 1-MT significantly increased renal injury and glomerular IgA accumulation and up-regulated Th17/Treg and Th17-related cytokine expression in IgAN mice, while ISS-ODN significantly decreased renal injury and glomerular IgA accumulation, down-regulated Th17/Treg expression and inhibited Th17-related cytokine expression in IgAN mice. In conclusion, IDO was involved in the occurrence and progress of IgAN by regulating the Th17/ Treg balance.

• MeSH
• buňky Th17 imunologie   MeSH
• cytokiny metabolismus   MeSH
• IgA nefropatie enzymologie   imunologie   MeSH
• imunita * MeSH
• indolamin-2,3,-dioxygenasa metabolismus   MeSH
• ledviny zranění   metabolismus   patologie   MeSH
• myši inbrední BALB C MeSH
• regulační T-lymfocyty imunologie   MeSH
• signální transdukce MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Regulatory T cells (Treg) are a specialized subpopulation of T cells that act to suppress inadequate immune response. Psoriasis is recognized as a T -cell driven immune-mediated systemic inflammatory disease with skin manifestation. Effective therapeutical approach to treat psoriasis is Goeckerman therapy (GT ). The aim of this study was to compare the number of Treg in the peripheral blood of 27 psoriatic patients and 19 controls and to evaluate the influence of GT on Treg population in peripheral blood of patients with psoriasis. There was no significant difference in the relative number of Treg cells in the peripheral blood of healthy blood donors and patients with psoriasis before initiation of GT (P = 0.2668). In contrary, the relative number of Treg cells in peripheral blood of patients with psoriasis after GT was significantly higher than those found in healthy blood donors (P = 0.0019). Moreover, the relative number of Treg is significantly increased in psoriatic patients after Goeckerman therapy compared to the pre-treatment level (P = 0.0042). In conclusion, this significant increase in Treg count after GT is probably associated with amelioration of inflammation by GT , as disease activity expressed as PASI decreased in our patients by GT (P = 0.0001).

• MeSH
• dehet uhelný terapeutické užití   MeSH
• dermatologické látky terapeutické užití   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• počet lymfocytů MeSH
• psoriáza imunologie   terapie   MeSH
• regulační T-lymfocyty imunologie   MeSH
• terapie ultrafialovými paprsky MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH

Úvod: Vliv eikospentaneové kyseliny a dokosahexaneové kyseliny na imunitní reakce je studován velmi intenzivně. Cílem studie bylo zjistit, zda-li ovlivňuje DHA a EPA hladiny vybraných cytokinů Th1 odpovědi (IL-2, IL12-p70 a INF-g), a Th2 odpovědi (IL-4 a IL-6) a regulační cytokiny (IL- 10 a TGF-β1) a srovnání těchto změn u nemocných po odstranění tonzil pro chronický zánět (včetně infekce H. pylori). Materiál a metodika: Pacienti byli rozděleni do tří hlavních skupin a jedné kontrolní skupiny. Odběry byly provedeny před zahájením operace nebo před začátkem podávání EPA a DHA. Po 15 týdnech byl prováděn druhý odběr. Dávkování 540 mg EPA a 360 mg DHA bylo rozděleno do tří dávek denně. Ze získaných vzorků krvi byla odebrána plazma ke stanovení cytokinů. Jejich koncentrace byla následně změřena metodou protilátkových čipů Quantibody Custom Arrays. Statistické zpracování proběhlo za pomoci programu StatGraphics multifaktoriální analýzou ANOVA. Výsledky: Statisticky významná změna hladiny byla prokázána u cytokinu IL12-p70, kde se významnost potvrdila souběžně v obou částech měření. V první části byla zaznamenána signifikance p=0,04, a to mezi jednotlivými skupinami. V druhé části se objevil signifikantní výsledek (p=0,01), a to mezi stavem před a po podání EPA a DHA. Změna hladiny byla zjištěna i u odpovědi TH2, a to IL-6 po podávání EPA a DHA (korelační koeficient 0,48) a IL-4, kde jsou změny výraznější (korelační koeficient 0,77). Závěr: Cytokin IL12-p70 lze považovat za nejvíce ovlivněný podáním EPA a DHA a může mít vliv na odpověď Th1 a stimulaci Nk buněk.

Introduction: The effect of eikospentan acid (EPA) and dokosahexan acid (DHA) on immune reactions was very intensely studied. The aim of this study was to clarify the impact of chronic Helicobacter pylori infection and EPA and DHA levels on Th1 cytokines (IL-2, IL12-p70, INF-g), Th2 cytokines (IL-4, IL-6) and T reg cytokines (IL-10, TGF-b1) in patient after tonsillectomy. Materials and methods: Patients were sorted into three main groups and one control group. Sampling was performed before the start of surgery or before the start of EPA and DHA administration. The second sampling was performed after 15 weeks in all main groups. The daily dosage of 540 mg of EPA and 360 mg of DHA was divides into three doses . The cytokines were analysed from the blood plasma. The concentation of the cytokines was quantified by Quantibody Custom Array. Statistical analysis was performed by using StatGraphics programme – multifactorial analysis ANOVA. Results: Statistically significant result was obtained in cytokine IL12-p70 in both measurements. In first sampling (2012) was the significance p=0.04 among the individual groups. In the second sampling the significance was p=0.01 in the phase before and after preparate administration. Dependence on IL-6 was prooved after the perparate admonistration (correlative coeficient 0.48), on IL-4 was dependence little bit higher (correlative coeficient 0.77). Conclusion: Cytokine IL12-p70 seems to be the main regulatory cytokine, thus it is possible to think about Th1 and NK cells stimulation.

• MeSH
• chronická nemoc MeSH
• infekce vyvolané Helicobacter pylori MeSH
• interferon gama imunologie   MeSH
• interleukin-12 imunologie   MeSH
• interleukin-4 imunologie   MeSH
• interleukin-6 imunologie   MeSH
• kyselina eikosapentaenová * aplikace a dávkování   MeSH
• kyseliny dokosahexaenové * aplikace a dávkování   MeSH
• lidé MeSH
• pilotní projekty MeSH
• regresní analýza MeSH
• Th1 buňky imunologie   MeSH
• Th2 buňky imunologie   MeSH
• tonzilektomie MeSH
• tonzilitida * chirurgie   imunologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

Chlamydia psittaci pneumonia (CPP) is a lung disease caused by the infection with the Chla-mydia psittaci bacterium, which can lead to severe acute respiratory distress syndrome and systemic symptoms. This study explored the specific mechanisms underlying the impact of reactive oxygen species (ROS) on the Th17/Treg balance in CPP. The levels of ROS and the differentiation ratio of Th17/Treg in the peripheral blood of healthy individuals and CPP patients were measured using ELISA and flow cytometry, respectively. The association between the ROS levels and Th17/Treg was assessed using Pearson correlation analysis. The ROS levels and the Th17/Treg ratio were measured in CD4+ T cells following H2O2 treatment and NLRP3 inhibition. The effects of H2O2 treatment and NLRP3 inhibition on the NLRP3/IL-1β/caspase-1 pathway were observed using immunoblotting. Compared to the healthy group, the CPP group exhibited increased levels of ROS in the peripheral blood, an elevated ratio of Th17 differentiation, and a decreased ratio of Treg differentiation. ROS levels were positively correlated with the Th17 cell proportion but negatively correlated with the Treg cell proportion. The ROS levels and NLRP3/IL-1β/caspase-1 expression were up-regulated in CD4+ T cells after H2O2 treatment. Furthermore, there was an increase in Th17 differentiation and a decrease in Treg differentiation. Conversely, the NLRP3/IL-1β/caspase-1 pathway inhibition reversed the effects of H2O2 treatment, with no significant change in the ROS levels. ROS regulates the Th17/Treg balance in CPP, possibly through the NLRP3/IL-1β/caspase-1 pathway. This study provides a new perspective on the development of immunotherapy for CPP.

• MeSH
• buněčná diferenciace * účinky léků   MeSH
• buňky Th17 * imunologie   metabolismus   MeSH
• Chlamydophila psittaci * MeSH
• dospělí MeSH
• interleukin-1beta * metabolismus   MeSH
• kaspasa 1 * metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• peroxid vodíku metabolismus   MeSH
• protein NLRP3 * metabolismus   MeSH
• psitakóza MeSH
• reaktivní formy kyslíku * metabolismus   MeSH
• regulační T-lymfocyty * imunologie   MeSH
• signální transdukce MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The development of thymic regulatory T cells (Treg) is mediated by Aire-regulated self-antigen presentation on medullary thymic epithelial cells (mTECs) and dendritic cells (DCs), but the cooperation between these cells is still poorly understood. Here we show that signaling through Toll-like receptors (TLR) expressed on mTECs regulates the production of specific chemokines and other genes associated with post-Aire mTEC development. Using single-cell RNA-sequencing, we identify a new thymic CD14+Sirpα+ population of monocyte-derived dendritic cells (CD14+moDC) that are enriched in the thymic medulla and effectively acquire mTEC-derived antigens in response to the above chemokines. Consistently, the cellularity of CD14+moDC is diminished in mice with MyD88-deficient TECs, in which the frequency and functionality of thymic CD25+Foxp3+ Tregs are decreased, leading to aggravated mouse experimental colitis. Thus, our findings describe a TLR-dependent function of mTECs for the recruitment of CD14+moDC, the generation of Tregs, and thereby the establishment of central tolerance.

• MeSH
• analýza jednotlivých buněk MeSH
• antigeny CD14 metabolismus   MeSH
• autoantigeny imunologie   MeSH
• autotolerance MeSH
• chemokiny imunologie   metabolismus   MeSH
• dendritické buňky imunologie   MeSH
• epitelové buňky imunologie   metabolismus   MeSH
• kolitida imunologie   MeSH
• modely nemocí na zvířatech MeSH
• myši MeSH
• převzatá imunita MeSH
• prezentace antigenu MeSH
• průtoková cytometrie MeSH
• receptory imunologické metabolismus   MeSH
• regulační T-lymfocyty imunologie   transplantace   MeSH
• sekvenční analýza RNA MeSH
• separace buněk MeSH
• signální transdukce imunologie   MeSH
• thymus cytologie   imunologie   MeSH
• toll-like receptory metabolismus   MeSH
• upregulace MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Celiac disease (CeD) manifests with autoimmune intestinal inflammation from gluten and genetic predisposition linked to human leukocyte antigen class-II (HLA-II) gene variants. Antigen-presenting cells facilitate gluten exposition through the interaction of their surface major histocompatibility complex (MHC) with the T cell receptor (TCR) on T lymphocytes. This fundamental mechanism of adaptive immunity has broadened upon recognition of extracellular exosomal MHC, raising awareness of an alternative means for antigen presentation. This study demonstrates that conditioned growth media (CGM) previously exposed to monocyte-derived dendritic cells from CeD significantly downregulates the CD3+ lineage marker of control T cells. Such increased activation was reflected in their elevated IL-2 secretion. Exosome localization motif identification and quantification within HLA-DQA1 and HLA-DQB1 transcripts highlighted their significant prevalence within HLA-DQB1 alleles associated with CeD susceptibility. Flow cytometry revealed the strong correlation between HLA-DQ and the CD63 exosomal marker in T cells exposed to CGM from MoDCs sourced from CeD patients. This resulted in lower concentrations of CD25+ CD127- T cells, suggestive of their compromised induction to T-regulatory cells associated with CeD homeostasis. This foremost comparative study deciphered the genomic basis and extracellular exosomal effects of HLA transfer on T lymphocytes in the context of CeD, offering greater insight into this auto-immune disease.

• MeSH
• alely MeSH
• celiakie * MeSH
• gluteny genetika   MeSH
• HLA-DQ antigeny genetika   MeSH
• lidé MeSH
• regulační T-lymfocyty MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: To analyze changes in T-helper (Th) subsets, T-regulatory (Treg) cell percentages and function, and mRNA levels of immunologically relevant molecules during a 24-month follow-up after alemtuzumab treatment in patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: Multicenter follow-up of 29 alemtuzumab-treated patients with RRMS in the Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS) I and CARE-MS II trials. Peripheral blood (PB) samples were obtained at months 0, 6, 12, 18, and 24. We evaluated (1) mRNA levels of 26 immunologic molecules (cytokines, chemokines, chemokine receptors, and transcriptional factors); (2) Th1, Th17, and Treg cell percentages; and (3) myelin basic protein (MBP)-specific Treg suppressor activity. RESULTS: We observed 12 relapses in 9 patients. mRNA levels of the anti-inflammatory cytokines interleukin (IL)-10, IL-27, and transforming growth factor-β persistently increased whereas those of proinflammatory molecules related to the Th1 or Th17 subsets persistently decreased after alemtuzumab administration throughout the follow-up period. PB CD4+ cell percentage remained significantly lower than baseline while that of Th1 and Th17 cells did not significantly change. A significant increase in Treg cell percentage was observed at month 24 and was accompanied by an increase in Treg cell suppressive activity against MBP-specific Th1 and Th17 cells. CONCLUSIONS: The long-lasting therapeutic benefit of alemtuzumab in RRMS may involve a shift in the cytokine balance towards inhibition of inflammation associated with a reconstitution of the PB CD4+ T-cell subsets that includes expansion of Treg cells with increased suppressive function.

• Publikační typ
• časopisecké články MeSH