New mechanisms regulating human Th1 and Th2 cell differentiation

Selective development of human T helper (Th) cells into functionally distinct Th1 and Th2 subtypes plays an essential role in the host immune response towards pathogens. However, abnormal function or differentiation of these cells can lead to development of various autoimmune diseases as well as asthma and allergy. Therefore, identification of key factors and the molecular mechanisms mediating Th1 and Th2 cell differentiation is important for understanding the molecular mechanisms of these diseases. The goal of this study was to identify novel factors involved in the regulation of Th1 and Th2 differentiation processes. A new method was optimized for enrichment of transiently transfected resting human primary T lymphocytes, that allowed the study of the influence of genes of interest in human Th1/Th2 cell differentiation and other primary Th cell functions. Functional characterization of PRELI, a novel activation-induced protein in human Th cells, identified it as a mitochondrial protein involved in the regulation of Th cell differentiation and apoptosis. By influencing the intracellular redox state, PRELI induces mitochondrial apoptosis pathway and downregulates STAT6 and Th2 differentiation. The data suggested that Calpain, an oxidative stress induced cysteine protease, is involved as a mediator in PRELI-induced downregulation of STAT6. PIM serine/threonine-specific kinases were identified as new regulators of human Th1 cell differentiation. PIM1 and PIM2 kinases were shown to be preferentially expressed in Th1 cells as compared to Th2 cells. RNA interference studies showed that PIM kinases enhance the production of IFN, the hallmark cytokine produced by Th1 cells. They also induce the expression of the key Th1-driving factor T-bet and the IL-12 signaling pathway during early phases of Th1 cell differentiation. Taken together, new regulators of human T helper cell differentiation were identified in this study, which provides new insights into the signaling mechanisms controlling the selective activation of human Th cell subsets.Siirretty Doriast

PRELI is a mitochondrial regulator of human primary T-helper cell apoptosis, STAT6, and Th2-cell differentiation

The identification of novel factors regulating human T helper (Th)–cell differentiation into functionally distinct Th1 and Th2 subsets is important for understanding the mechanisms behind human autoimmune and allergic diseases. We have identified a protein of relevant evolutionary and lymphoid interest (PRELI), a novel protein that induces oxidative stress and a mitochondrial apoptosis pathway in human primary Th cells. We also demonstrated that PRELI inhibits Th2-cell development and down-regulates signal transducer and activator of transcription 6 (STAT6), a key transcription factor driving Th2 differentiation. Our data suggest that calpain, an oxidative stress–induced cysteine protease, is involved in the PRELI-induced down-regulation of STAT6. Moreover, we observed that a strong T-cell receptor (TCR) stimulus induces expression of PRELI and inhibits Th2 development. Our results suggest that PRELI is involved in a mechanism wherein the strength of the TCR stimulus influences the polarization of Th cells. This study identifies PRELI as a novel factor influencing the human primary Th-cell death and differentiation

Insuliinin pistotekniikka - Opetusvideo hoitotyön koulutusohjelman opiskelijoille

Diabetes on maailmanlaajuisesti yksi sairastetuimmista taudeista, joka lisääntyy nopeasti. Diabetes on yleisnimitys useille sairauksille, joita kaikkia yhdistää aineenvaihduntahäiriön aiheuttama verensokeritason nousu. Insuliini on elimistön ainoa verensokeria laskeva hormoni, jolla on tärkeä rooli myös energia-aineenvaihdunnan säätelemisessä. Diabeteksessa elimistön oma insuliinin tuotanto on häiriintynyt. Jos haima ei tuota insuliinia riittävästi elimistön tarpeisiin, niin puuttuva insuliini korvataan yleisesti ihonalaisilla pistoksilla. Insuliinin imeytymisen kannalta on tärkeää, että insuliininpistotekniikka on hallinnassa. Tässä toiminnallisessa opinnäytetyössä käsitellään yleisesti diabetesta, insuliinihoitoa ja insuliinin pistotekniikkaa sekä siihen liittyviä asioita. Toiminnallinen osuus koostuu insuliinin pistotekniikan opetusvideosta, jossa näytetään insuliinin pistäminen insuliinikynällä itselle reiteen sekä insuliiniruiskulla toiselle vatsaan. Toiminnallinen osuus tehtiin yhdessä kahden Karelia-ammattikorkeakoulun media-alan opiskelijan kanssa. Opinnäytetyön tarkoituksena on lisätä hoitotyön opiskelijoiden tietoutta insuliinin pistotekniikasta, -välineistä ja -paikoista. Tämän opinnäytetyön tehtävänä oli tuottaa opetusvideo hoitotyön koulutusohjelman opiskelijoille muun opetusmateriaalin tueksi insuliininpistotekniikasta. Opetusvideo sisältää selkeät, yksinkertaiset ja ajankohtaiset ohjeet insuliinin pistämisestä. Jatkokehitysehdotuksena opetusvideon tueksi voisi tehdä kirjalliset ohjeet tai tekstityksen videoon ja selvittää opetusvideon vaikutuksia oppimiseen. Jatkossa opinnäytetyön voisi tehdä insuliinihoidon toteutukseen liittyvistä haasteista esimerkiksi lasten, kehitysvammaisten tai vanhusten kohdalla.Diabetes is one of the most common diseases worldwide and is becoming more common rapidly. Diabetes is a common term for various disorders related to a metabolic disorder caused by a rise in blood glucose level. Insulin is the body’s only hormone that lowers blood glucose level; it also plays an important role in regulating energy metabolism. When a person suffers from diabetes, the body’s insulin production is impaired. If the pancreas does not produce sufficient insulin for the body’s needs, the lack of insulin is usually provided by subcutaneous injections. For the absorption of insulin, the correct injection technique is vital. This practice-based thesis discusses diabetes in general, insulin treatment, injection technique and related issues. The practical part is an educational video that shows how to inject insulin into one’s own thigh with an insulin pen as well as with a syringe into another person’s abdomen. The video was produced in co-operation with two Media Studies students at the Karelia University of Applied Sciences. The aim of the thesis was to increase nursing students’ awareness of insulin injection technique, instruments and sites. The purpose of this thesis was to produce an educational video for nursing students presenting clear, simple and up-to-date instructions for injecting insulin and to support other related educational material. As a further development idea, written instructions or subtitles could be created and the impact on learning could be investigated. In the future, a thesis about challenges in implementing insulin treatment among children, disabled or older people could be carried out

Genome-wide profiling of interleukin-4 and STAT6 transcription F factor regulation of human Th2 cell programming

SummaryDissecting the molecular mechanisms by which T helper (Th) cells differentiate to effector Th2 cells is important for understanding the pathogenesis of immune-mediated diseases, such as asthma and allergy. Because the STAT6 transcription factor is an upstream mediator required for interleukin-4 (IL-4)-induced Th2 cell differentiation, its targets include genes important for this process. Using primary human CD4+ T cells, and by blocking STAT6 with RNAi, we identified a number of direct and indirect targets of STAT6 with ChIP sequencing. The integration of these data sets with detailed kinetics of IL-4-driven transcriptional changes showed that STAT6 was predominantly needed for the activation of transcription leading to the Th2 cell phenotype. This integrated genome-wide data on IL-4- and STAT6-mediated transcription provide a unique resource for studies on Th cell differentiation and, in particular, for designing interventions of human Th2 cell responses