STING gain-of-function mice developed an interferon-independent SCID phenotype with a T-cell, B-cell, and natural killer cell developmental defect and hypogammaglobulinemia that is associated with signs of inflammation in lungs and kidneys. Only the intrinsic proliferative defect of T cells was partially interferon dependent.

Systemic lupus erythematosus (SLE) is a severe and heterogeneous autoimmune disease with a complex genetic etiology, characterized by the production of various pathogenic autoantibodies, which participate in end-organ damages. The majority of human SLE occurs in adults as a polygenic disease, and clinical flares interspersed with silent phases of various lengths characterize the usual evolution of the disease in time. Trying to understand the mechanism of the different phenotypic traits of the disease, and considering the central role of B cells in SLE, we previously performed a detailed wide analysis of gene expression variation in B cells from quiescent SLE patients. This analysis pointed out an overexpression of TRIB1. TRIB1 is a pseudokinase that has been implicated in the development of leukemia and also metabolic disorders. It is hypothesized that Trib1 plays an adapter or scaffold function in signaling pathways, notably in MAPK pathways. Therefore, we planned to understand the functional significance of TRIB1 overexpression in B cells in SLE. We produced a new knock-in model with B-cell-specific overexpression of Trib1. We showed that overexpression of Trib1 specifically in B cells does not impact B cell development nor induce any development of SLE symptoms in the mice. By contrast, Trib1 has a negative regulatory function on the production of immunoglobulins, notably IgG1, but also on the production of autoantibodies in an induced model. We observed a decrease of Erk activation in BCR-stimulated Trib1 overexpressing B cells. Finally, we searched for Trib1 partners in B cells by proteomic analysis in order to explore the regulatory function of Trib1 in B cells. Interestingly, we find an interaction between Trib1 and CD72, a negative regulator of B cells whose deficiency in mice leads to the development of autoimmunity. In conclusion, the overexpression of Trib1 could be one of the molecular pathways implicated in the negative regulation of B cells during SLE.

Los individuos con síndrome de Down presentan alteraciones sistémicas y clínicas que ayudan al desarrollo de la enfermedad periodontal, en especial gingivitis úlceronecrotizante aguda y periodontitis rápida progresiva. Las causas del desarrollo son alteraciones inmunológicas, especialmente por los linfocitos T; disfunción tiroidea, leucemia linfocítica aguda, alteraciones genéticas con características faciales, orales y anomalías en el desarrollo; alteraciones microbiológicas (presencia de A. actÍnomycetemcomÍtansy P Íntermedki¡ asociadas a una mala higiene oral muchas veces relacionada con el retardo mental. Al revisor los factores que condicionan la enfermedad periodontal en individuos con síndrome de Down, se observa que hay una predisposición a la enfermedad periodontal, en la cual los factores genéticos e inmunológicos son los principales precursores de esta enfermedad de rápida progresión, los factores microbiológicos y la pobre higiene oral actúan como factores contribuyentes del desarrollo y progresión, como factores exógenos. [Delgado E, Díaz NE, Chacón CM, Delgado R, Flórez LT. Factores que condicionan la enfermedad periodontal en individuos con síndrome de Down. Foctors thot Predispose the Periodontol Condition in Down Syndrome Individuols ABSTRACTPeriodontal disease represents a disequilibrium between factors such as causes and the host at the dento gingival union. Down syndrome individuals present systemic alterations as well as clinical ones which help the outcome of periodontal disease, specially acute ulceronecrotic gingivitis and rapidly progressive periodontitis. The causes of outcome are due to immune alterations, specially by T cells, thyroid disfunction, acute linfocyte leukemia, genetic alterations with facial and oral characteristics, and growth anomalies; microbiological alterations, poor oral hygiene. The revision of factors that cause periodontal disease in individuals with Down syndrome, state a predisposition to the disease itself in which genetic and immune factors are the main precursors of this rapidly progressive disease, and microbiological factors as well as hygiene act like contributives to the outcome and progression as externa! factors. The monograph work was made through bibliographical sources obtaining a revision about the factors that condition the periodontal disease in Down syndrome individuals.