Modulation of HLA antigen expression in the endocrine cells of the human pancreas

HLA Class II molecules are surface glycoproteins which are essential in the initiation of immune responses to specific antigens. Work on thyroid autoimmune disease has suggested that the induction of Class II expression in epithelial cells such as endocrine cells, which are normally Class II negative, may contribute to the development of autoimmunity. In recent onset Type 1 diabetes, islet β cells, the target of the autoimmune process, selectively express Class II antigens. The regulation of Class II expression by β cells is therefore of great potential interest for understanding the pathogenesis of Type 1 diabetes. Given the inaccessibility of the endocrine islets in the diabetic pancreas, the approach adopted here has been to search for those mediators capable of inducing Class II in the human β cells in vitro and then, on the basis of their characteristics, surmise whether these mediators could correspond to those acting in vivo. Initially, considerable work was carried out to establish a culture system in which the expression of HLA by human islet cells (adult and foetal) could be studied with simultaneous identification of the cell type. As an internal control exocrine/ductal cells were also characterized and monitored. In contrast to most other cell types, islet β cells were not stimulated to express Class II by IFN-γ and thus the conditions under which this occurs have been elusive. Many other mediators tested were also unable to induce Class II expression by islet cells. Finally, it was found that IFN-γ in combination with either TNF-α or TNF-β induced islet cell Class II expression (DR, DP and DQ) in a dose related manner. As it has been shown that in the pancreata of newly diagnosed Type 1 diabetes patients the four types of islet cells strongly hyperexpress HLA Class I, the regulation of Class I expression was also studied. The in vitro experiments showed that all three types of IFNs, i.e. α, β and γ, have the capability of enhancing Class I expression in the islet cells. These findings strengthen the previous histopathological observations on the pancreas of diabetic individuals and also point to a possible sequence of events leading to this phenomenon in vivo

Implementació d'un Laboratori d'Habilitats Clíniques

Podeu consultar la Vuitena trobada de professorat de Ciències de la Salut completa a: http://hdl.handle.net/2445/66524L’ensenyament en Ciències de la Salut complementa la formació teòrica amb la realització de pràctiques clíniques. Els nous plans d’estudis contemplen les competències i habilitats obligatòries a adquirir. El seu aprenentatge es complexa, intens i perllongat en el temps, integrant coneixements teòrics i habilitat en el maneig de les diferents tècniques. Els maniquins simuladors permeten l’ensenyament i entrenament sense estres per l’alumne i el professorat i sense riscos ple malalt. L’any 2005 es va crear al nostre Campus un Laboratori d’habilitats Clíniques (LHC)..

Efferocytosis promotes suppressive effects on dendritic cells through prostaglandin E2 production in the context of autoimmunity

Introduction: Efferocytosis is a crucial process by which apoptotic cells are cleared by phagocytes, maintaining immune tolerance to self in the absence of inflammation. Peripheral tolerance, lost in autoimmune processes, may be restored by the administration of autologous dendritic cells loaded with islet apoptotic cells in experimental type 1 diabetes. Objective: To evaluate tolerogenic properties in dendritic cells induced by the clearance of apoptotic islet cells, thus explaining the re-establishment of tolerance in a context of autoimmunity. Methods: Bone marrow derived dendritic cells from non-obese diabetic mice, a model of autoimmune diabetes, were generated and pulsed with islet apoptotic cells. The ability of these cells to induce autologous T cell proliferation and to suppress mature dendritic cell function was assessed, together with cytokine production. Microarray experiments were performed using dendritic cells to identify differentially expressed genes after efferocytosis. Results: Molecular and functional changes in dendritic cells after the capture of apoptotic cells were observed. 1) Impaired ability of dendritic cells to stimulate autologous T cell proliferation after the capture of apoptotic cells even after proinflammatory stimuli, with a cytokine profile typical for immature dendritic cells. 2) Suppressive ability of mature dendritic cell function. 3) Microarray-based gene expression profiling of dendritic cells showed differential expression of genes involved in antigen processing and presentation after efferocytosis. 4) Prostaglandin E2 increased production was responsible for immunosuppressive mechanism of dendritic cells after the capture of apoptotic cells. Conclusions: The tolerogenic behaviour of dendritic cells after islet cells efferocytosis points to a mechanism of silencing potential autoreactive T cells in the microenvironment of autoimmunity. Our results suggest that dendritic cells may be programmed to induce specific immune tolerance using apoptotic cells; this is a viable strategy for a variety of autoimmune diseases.This work was supported by grants from the Fondo de Investigaciones Sanitarias (PS09/00253 and PI12/00195) of the Carlos III Institute of Health, www.isciii.es. RP was supported by the Instituto de Salud Carlos III of the Spanish National Institute of Health (FIS05/00418). MVP is funded by the stabilization program of Miguel Servet biomedical researchers and RMA by the program of research technicians of the Instituto de Salud Carlos III and Direcció d’Estrategia i Coordinacio, Health Dept. of the Catalonian Government. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Experiència de flexibilitat metodològica en el procés d'ensenyament-aprenentatge. El cas de l'assignatura del grau de Farmàcia 'Biomembranes: estudis fisicoquímics'

Es descriu l'experiència realitzada en l'assignatura optativa Biomembranes: estudis fisicoquímics del Grau de Farmàcia de la UB. Aquest aspecte comporta formar un grup no molt nombrós d'estudiants i permet realitzar experiències metodològiques noves introduint aspectes de flexibilitat per a estudiants i professors. Es van establir els objectius competencials i es va dissenyar un programa flexible respecte a continguts, a activitats i dimensió espai-temps amb resultats satisfactoris

Activation of the Monocyte/Macrophage System and Abnormal Blood Levels of Lymphocyte Subpopulations in Individuals with Autism Spectrum Disorder: A Systematic Review and Meta-Analysis

Inflammation; Lymphocytes; MonocytesInflamació; Limfòcits; MonòcitsInflamación; Linfocitos; MonocitosAutism spectrum disorder (ASD) is a neurodevelopmental condition with a so far unknown etiology. Increasing evidence suggests that a state of systemic low-grade inflammation may be involved in the pathophysiology of this condition. However, studies investigating peripheral blood levels of immune cells, and/or of immune cell activation markers such as neopterin are lacking and have provided mixed findings. We performed a systematic review and meta-analysis of studies comparing total and differential white blood cell (WBC) counts, blood levels of lymphocyte subpopulations and of neopterin between individuals with ASD and typically developing (TD) controls (PROSPERO registration number: CRD CRD42019146472). Online searches covered publications from 1 January 1994 until 1 March 2022. Out of 1170 publication records identified, 25 studies were finally included. Random-effects meta-analyses were carried out, and sensitivity analyses were performed to control for potential moderators. Results: Individuals with ASD showed a significantly higher WBC count (k = 10, g = 0.29, p = 0.001, I2 = 34%), significantly higher levels of neutrophils (k = 6, g = 0.29, p = 0.005, I2 = 31%), monocytes (k = 11, g = 0.35, p < 0.001, I2 = 54%), NK cells (k = 7, g = 0.36, p = 0.037, I2 = 67%), Tc cells (k = 4, g = 0.73, p = 0.021, I2 = 82%), and a significantly lower Th/Tc cells ratio (k = 3, g = −0.42, p = 0.008, I2 = 0%), compared to TD controls. Subjects with ASD were also characterized by a significantly higher neutrophil-to-lymphocyte ratio (NLR) (k = 4, g = 0.69, p = 0.040, I2 = 90%), and significantly higher neopterin levels (k = 3, g = 1.16, p = 0.001, I2 = 97%) compared to TD controls. No significant differences were found with respect to the levels of lymphocytes, B cells, Th cells, Treg cells, and Th17 cells. Sensitivity analysis suggested that the findings for monocyte and neutrophil levels were robust, and independent of other factors, such as medication status, diagnostic criteria applied, and/or the difference in age or sex between subjects with ASD and TD controls. Taken together, our findings suggest the existence of a chronically (and systemically) activated inflammatory response system in, at least, a subgroup of individuals with ASD. This might have not only diagnostic, but also, therapeutic implications. However, larger longitudinal studies including more homogeneous samples and laboratory assessment methods and recording potential confounding factors such as body mass index, or the presence of comorbid psychiatric and/or medical conditions are urgently needed to confirm the findings

Diagnostic value of different anti-citrullinated peptides antibodies in rheumatoid arthritis

Póster presentat al 6th European Workshop on Immune-Mediated Inflammatory Diseases, celebrat a Niça (França) el 201