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María Luna-Luna,1 Sergio Criales-Vera,2 Diana Medina-Leyte,1 Mariana Díaz-Zamudio,2 Adriana Flores-Zapata,1 David Cruz-Robles,1 Mauricio López-Meneses,3 Sergio Olvera-Cruz,3 Samuel Ramírez-Marroquín,4 Cristóbal Flores-Castillo,1 José Manuel Fragoso,1 Elizabeth Carreón-Torres,1 Jesús Vargas-Barrón,5 Gilberto Vargas-Alarcón,1 Óscar Pérez-Méndez1,6 1Molecular Biology, National Institute of Cardiology “Ignacio Chávez”, Mexico City, Mexico; 2Radiology, National Institute of Cardiology “Ignacio Chávez”, Mexico City, Mexico; 3Adult Cardiology, National Institute of Cardiology “Ignacio Chávez”, Mexico City, Mexico; 4Cardiothoracic Surgery, National Institute of Cardiology “Ignacio Chávez”, Mexico City, Mexico; 5Research Direction, National Institute of Cardiology “Ignacio Chávez”, Mexico City, Mexico; 6School of Engineering and Sciences, Tecnológico de Monterrey, Campus Monterrey, Mexico City, MexicoCorrespondence: Óscar Pérez-MéndezMolecular Biology Department, National Institute of Cardiology “Ignacio Chávez”, Mexico City, MexicoTel +52 55 55732911 ext 26300Email opmendez@yahoo.comPurpose: It has been proposed that the cardiovascular effects of obesity are related to epicardial adipose tissue (EAT), which seems to play an active role on the development and calcification of atherosclerotic plaques, but the mechanisms are still unknown. Therefore, the aim of this study was to determine whether the EAT expresses the genes of calcifying factors and whether such expression is associated with the body mass index (BMI) and with the presence of coronary artery calcium (CAC) in patients with coronary artery disease (CAD).Patients and Methods: Forty-three patients with CAD were enrolled specifically for this study, and their CAC score and EAT volume were determined by computed tomography. As the group of comparison, 41 patients with aortic valve stenosis and CAC = 0 were included (control group). A representative subgroup of 16 CAD patients and 23 controls were selected to obtain EAT biopsies during the chirurgical procedure from the atrio-interventricular groove. The mRNA expression of bone morphogenetic protein-2 and -4 (BMP-2, BMP-4), osteopontin (OPN), osteonectin (ON), and osteoprotegerin (OPG) in EAT was determined by qPCR.Results: The gene expression of OPN and BMP-2 was 70% and 52% higher in the EAT from CAD patients than that in controls, respectively, whereas the expression of OPG, ON, and BMP-4 was similar in both groups. The EAT volume positively correlated with OPG and with the BMI, suggesting a relationship of obesity with local higher expression of calcifying genes in the coronary territory. The logistic regression analysis showed that high levels of both OPN and BMP-2 increased about 6 and 8 times the odds of coronary calcification (CAC score > 0), respectively.Conclusion: EAT correlated with BMI and expressed the mRNA of calcifying genes but only OPN and BMP-2 expression was higher in CAD patients. Higher levels of both OPN and BMP-2 statistically determined the presence of calcium in coronary arteries of CAD patients.Keywords: obesity, adipocyte, calcifying proteins, coronary artery disease, atherosclerosis

Introduction. Crohn's disease is a chronic inflammatory condition that may affect any segment of the digestive tract, from the mouth to the anus, and belongs to the group of inflammatory intestinal diseases (IID). Diagnosis is based on clinical, biochemical, endoscopic, radiological, and histopathological correlation. Magnetic resonance enterography is a non-invasive diagnostic method that does not use ionizing radiation and complements the diagnosis of Crohn's disease; it provides information on the extent, degree of inflammation, and possible complications. It plays an important role in classification and surgical planning. Objective. Describe findings by magnetic resonance enterography in Crohn's disease and conduct a review of the specialized literature. Material and methods. A cross-sectional, descriptive study was conducted. All patients with Crohn's disease who were admitted for consultation at the Salvador Zubiran National Institute of Medical Science and Nutrition Department of Gastroenterology Inflammatory Intestinal Disease Clinic, in the period October 2011 through April 2012 were included. All the patients underwent clinical evaluation, laboratory studies, and magnetic resonance enterography. Results. Magnetic resonance enterography found signs of active disease in 46.6% of the patients. The most common manifestations were wall thickening (80%), alteration of mucosal pattern (73%), and reinforcement of the wall (60%). The segment most commonly involved was the ileum (60%). Conclusions. Magnetic resonance may provide anatomic details, functional observations, and information in real time without the use of ionizing radiation in evaluation of Crohn's disease. [ABSTRACT FROM AUTHOR]

Dual-energy computed angiotomography is capable of producing images which potentially provide information on pulmonary perfusion. Recent publications have shown promising results in application of this technique to prove perfusion defects in patients with acute pulmonary thromboembolism; however, information on its usefulness in patients with chronic pulmonary thromboembolism is scant. OBJECTIVE: determine if there are changes in pulmonary perfusion, in patients with chronic pulmonary thromboembolism, demonstrable by dual-energy angiotomography. MATERIAL AND METHODS: a prospective study in consecutive patients referred to the tomography department with suspicion of chronic pulmonary thromboembolism at Instituto Nacional de Cardiología Ignacio Chavez. RESULTS: analysis by lobe found a significant difference in arterial perfusion between patients with chronic pulmonary thromboembolism and controls. In the delayed phase, greater perfusion was shown in patients with chronic pulmonary thromboembolism compared with controls; however, the difference was not significant. CONCLUSION: biphasic perfusion by dual-energy pulmonary angiotomography is a tool which helps prove and quantify the functional alterations found in patients with chronic pulmonary thromboembolism. This technique can be useful in patients who are candidates for thromboendarterectomy because collateral circulation, a favorable factor for prognosis, can be qualitatively proved. [ABSTRACT FROM AUTHOR]

Tetralogy of Fallot is the most common form of cyanotic congenital heart disease; its clinical manifestations vary depending on the degree of obstruction of the right ventricular outflow tract and its hemodynamic repercussion. Surgical treatment may be complete repair or palliative depending on the patient's condition. Doppler color echocardiogram is the diagnostic method of choice; however, angiotomography has recently become a useful tool for diagnosis and postoperative monitoring. Objective: review the specialized literature on diagnostic criteria for Tetralogy of Fallot and discuss the principal postoperative findings in computed angiotomography. Material and methods: exhaustive review of the specialized literature and selection of representative cases of patients with diagnosis of tetralogy of Fallot (with computed angiotomography) at Instituto Nacional de Cardiologia Ignacio Chavez. Conclusion: computed angiotomography has emerged as an additional tool for diagnosis and postoperative monitoring of patients with tetralogy of Fallot, especially in patients with inconclusive echocardiograms, in whom it is preferable to avoid the sedation required for evaluation by magnetic resonance. The radiologist must be familiar with the key signs for diagnosis of tetralogy of Fallot and for monitoring palliative or definitive surgical treatment. [ABSTRACT FROM AUTHOR]

In single coronary artery (SCA) anatomy, all coronary tributaries arise from a single ostium, providing perfusion to the entire myocardium. Coronary classification systems can facilitate the description of SCA anatomy. Aim: Evaluation of the applicability of Lipton classification and the Leiden Convention coronary coding system in SCA. Methods: All patients (n = 6209) who underwent computed tomography (CT) scanning between 2014 and 2018 were retrospectively examined for the presence of SCA and classified, according to Lipton classification and the Leiden Convention coronary coding system. Results: The prevalence of SCA was 0.51% (32/6209). Twenty-eight patients (87.5%) had coexisting congenital heart disease (CHD), most frequently pulmonary atresia (9/32, 28.1%). Ten patients (10/32, 31.25%) could not be classified with either the Leiden Convention or Lipton classification (pulmonary atresia n = 9, common arterial trunk (CAT) n = 1). In one case with CAT, Lipton classification, but not the Leiden Convention, could be applied. In two cases with the transposition of the great arteries and in two cases of double outlet right ventricle, the Leiden Convention, but not the Lipton classification, could be applied. Conclusions: Both classifications are useful to detail information about SCA. As Lipton classification was not developed for structural heart disease cases, in complex CHD with abnormal position of the great arteries, the Leiden Convention is better applicable. The use of both systems is limited in pulmonary atresia. In this scenario, it is better to provide a precise description of the coronary origin and associated characteristics that might affect treatment and prognosis.

The present study aimed to determine the effectiveness of sclerotherapy using NBCA (Histoacryl Blue®; B. Braun, Melgungen, Germany), with or without hydrodissection, for the treatment of simple renal cysts. Materials and Methods : Patients who presented to an interventional radiology clinic for the diagnosis of symptomatic renal cysts which had previously been identified at an outpatient clinic were selected for inclusion in this study. A total of 28 patients were randomly divided into 2 groups, based on whether or not they underwent hydrodissection along with ultrasound-guided NBCA-based sclerotherapy. Sonographs were performed at 0, 7, and 180 days post-procedure to record the residual volume of the renal cysts and to determine the efficacy of the procedure. Results: A total of 32 cysts in 28 patients were treated with sclerotherapy, 18 (64%) females and 10 (36%) males. The average age of the patients was 61.8 years (range: 33-89 years). All patients reported an improvement in symptoms associated with the existing renal cysts at 7 and 180 days post-procedure, and at 7 days post-procedure a statistically significant reduction in cyst volume was observed (all patients: 96.8%; group A: 96%; group B: 97.6%). The reduced cyst volume was still observed 180 days post-procedure (all patients: 98.6%; group A: 98.2%; group B: 98.9%). There was no significant difference between the two treatment groups. Conclusion: There is a significant and persistent reduction in the volume of renal cysts, in addition to an improvement of the associated symptoms, after treatment with NBCA-based sclerotherapy, with or without hydrodissection., Competing Interests: The authors declare that they have no conflicts of interests to this work. We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (© 2020 Shanghai Journal of Interventional Radiology Press. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.)

Lymphopenia is strongly associated with autoimmune diseases. The molecular mechanisms that link both phenomena are still unclear, but certain key pathways have been described. Central tolerance is as important as peripheral. In the earlier, epithelial and dendritic cells play a crucial role in the selection of clones. In the latter, regulatory T cells (Tregs) rise as inductors of anergy in order to prevent the development of autoimmune pathology. In lymphopenic conditions, T cells develop the process of lymphopenia-induced proliferation (LIP). A complex interaction between the major histocompatibility complex (MHC) and the T cell receptor (TCR) makes this process possible. Furthermore, IL-7 can act synergistically or in an independent manner to promote LIP. A lack of Transforming Growth Factor-β (TGF-β) was recently described as the second hit needed to develop autoimmunity in a lymphopenic microenvironment, given its actions in Tregs and its interaction with CTLA-4. Regarding autoimmune clinical scenarios, lymphopenia is related to both, systemic and organ-specific diseases. Thus, the molecular study of such patients has been limited and needs to be widened to the pathways shown here to be involved in the development of lymphopenia and autoimmunity., (Copyright © 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

Objective: Cardiac complications in infectious endocarditis (IE) are seen in nearly 50% of cases, and systemic complications may occur. The aim of the present study was to determine the characteristics of inpatients with IE who suffered acute neurologic complications and the factors associated with early mortality., Methods: From January 2004 to May 2010, we reviewed clinical and imaging charts of all of the patients diagnosed with IE who presented a deficit suggesting a neurologic complication evaluated with Computed Tomography or Magnetic Resonance within the first week. This was a descriptive and retrolective study., Results: Among 325 cases with IE, we included 35 patients (10.7%) [19 males (54%), mean age 44-years-old]. The most common underlying cardiac disease was rheumatic valvulopathy (n=8, 22.8%). Twenty patients survived (57.2%, group A) and 15 patients died (42.8%, group B) during hospitalization. The main cause of death was septic shock (n=7, 20%). There was no statistical difference among groups concerning clinical presentation, vegetation size, infectious agent and vascular territory. The overall number of lesions was significantly higher in group B (3.1 vs. 1.6, p=0.005) and moderate to severe cerebral edema were more frequent (p=0.09). Sixteen patients (45.7%) (12 in group A and 4 in group B, p=0.05) were treated by cardiac surgery. Only two patients had a favorable outcome with conservative treatment (5.7%)., Conclusions: In patients with IE complicated with stroke, the number of lesions observed in neuroimaging examinations and conservative treatment were associated with higher in-hospital mortality., (Copyright © 2014 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.)

Background: Laparoscopic Roux-en-Y gastric bypass (LRYGB) may be a technically challenging surgical technique when features such as thick abdominal wall and increased liver volume are present. Very low calorie diets in the form of liquid meal replacements given 6 weeks prior to surgery have proven to decrease liver volume. The aim of our study was to assess the effect of a 6-week preoperative low calorie/regular diet on liver volume and body weight in morbidly obese patients., Methods: A pilot study was carried out in 20 morbidly obese patients with an 800-kcal diet for 6 weeks. They were followed weekly to ensure proper compliance. CT scan was used for determining liver volume every 2 weeks in order to assess the impact of the diet. Baseline values were taken as controls for every patient as tied measures. Statistical analysis was suitable to variable scaling and performed using SPSS v. 20.0. Parametric and non-parametric test for tied measures were done. Any p value lesser than 0.05 or 5% was considered as statistically significant., Results: Twenty patients adhered to the diet intervention for 6 weeks prior to LRYGB. Median ± SD age was 34.5 ± 11.5 years and 17 were female (85%). Heart rate and blood pressure did not vary across the study. Initial median ± SD BMI was 46.02 ± 5.29 kg/m2 (range 38.7-54.8). Repeated and tied measurements across the 6 weeks of treatment within individuals resulted statistically significant for reducing BMI (p < 0.0001). CT scan assessed liver volume initially as a control and in weeks 2, 4 and 6. Parametric and non-parametric assessment for multiple measurements also showed statistical significance among these values (p < 0.0001). Diet tolerability was additionally evaluated with a questionnaire showing more than 80% of acceptability with discrete rates of nausea (15%) and diarrhoea (15%)., Conclusions: Based on our results, we demonstrated that a very low calorie diet with home ingredients is capable for effectively reducing body weight and liver size in morbidly obese patients. This relatively short intervention (4 to 6 weeks) was accomplished in all our patients with a high frequency of compliance and a low rate of secondary effects.

Objective: To analyze whether the expression and modulation of T cell receptor (TCR) signaling is dependent on Casitas B lineage lymphoma b (Cbl-b) in T cells from patients with systemic lupus erythematosus (SLE) upon stimulation with a tolerogenic substance., Methods: Peripheral blood mononuclear cells were obtained from 20 patients with SLE (active disease or in remission) and 20 healthy controls. Levels of Cbl-b expression were measured using reverse transcription-polymerase chain reaction and Western blotting in peripheral CD4+ T cells from SLE patients and healthy controls upon anergy induction. Cell proliferation was measured using the carboxyfluorescein diacetate succinimidyl ester dilution method. Cytokine production was analyzed by luminometry, and surface expression of activation markers was assessed by flow cytometry. Transfection assays were performed to induce overexpression of Cbl-b, and phosphorylation of TCR-associated kinases was evaluated., Results: CD4+ T cells from SLE patients displayed resistance to anergy (as evidenced by increased cell proliferation, interleukin-2 production, and expression of activation and costimulatory markers), and this was associated with altered Cbl-b expression. Upon ionomycin treatment, primary T cells showed enhanced MAPK activity and decreased Akt phosphorylation, which was representative of the anergic state. In T cells from lupus patients, Cbl-b overexpression led to increased expression of phosphorylated MAPK, thus indicating the reversibility of anergy resistance., Conclusion: These findings suggest that abnormal peripheral tolerance in SLE is caused by a deficiency in Cbl-b, and that this ubiquitin ligase plays a key role in regulating TCR signaling during the induction of peripheral tolerance., (Copyright © 2013 by the American College of Rheumatology.)

Systemic Sclerosis (SSc) is an autoimmune disease characterized by fibrosis and vasculopathy. A key feature is the presence of T cells in inflammatory lesions. To establish the differences in peripheral blood T helper (Th) subpopulations in diffuse cutaneous (dc) and limited cutaneous (lc) SSc patients, blood samples from 57 dcSSc and 78 lcSSc patients were obtained. Controls were collected from healthy volunteers (n = 16), active systemic lupus erythematosus (aSLE) patients (n = 13), and active rheumatoid arthritis (aRA) patients (n = 12). Mononuclear cells were analyzed by flow cytometry to determine Th1 (CD4+/IFN-γ+), Th2 (CD4+/IL-4+), Th17 (CD4+/IL-17+), and regulatory T cells (Tregs; CD4+/CD25+/Foxp3+) subsets. Th17 and Th1 subsets were increased in SSc groups versus healthy controls (P < 0.001) and aSLE patients (P < 0.001 for Th17 and P < 0.008 for Th1). Th2 cells were higher in dcSSc patients than in the healthy and aSLE groups (P = 0.03 and P = 0.009, respectively). Tregs were increased in the aRA group when compared with SSc patients and healthy controls (P ≤ 0.003). Patients with immunosuppressive treatment had lower numbers of Th17 and Th2 cells (P = 0.02). Our results shed further light into the preponderant role of Th17 and Th1 in patients with SSc. However, these findings certainly deserve to be studied in depth.

Abnormal production of interferon type I has been widely related to multiple autoimmune diseases, particularly systemic lupus erythematosus (SLE). It has been considered the molecular signature characterized by the overexpression of type I Interferon related genes in SLE patients. Among these, are the interferon regulatory factors (IRF). These transcription factors have been involved in the innate immune response, mainly the one related to the defense against viral infections; the development of immune cells and carcinogenesis. The role of IRF in autoimmune pathology has been addressed in diverse murine models. However, evidence in humans is quite scant. This review will focus on the evidence that supports the role of IRF in the development or susceptibility to autoimmune diseases. Specific emphasis will be made over the role of IRF-5 and IRF-7, since evidence of its association to the development of pathology, particularly systemic lupus erythematosus is the strongest., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Follicular helper T cells (T(FH)) have been implicated as a lineage that provides sufficient help to B cells in order to become professional antibody producers. This T helper subset is characterized by a distinctive cell-surface phenotype (CD4(+)CD57(+)CXCR5(+)) and cytokine profile (IL-21, IL-6, and IL-27) as well as transcriptional program (BCL-6, ICOS, and PD-1). Evidence supports the concept that T(FH) subset development, as well as for other lineages, is dependent on microenvironment cues that modulate a particular transcriptional program, susceptible to plasticity. Recently, it has been shown that BCL-6 and IL-21 act as master regulators for the development and function of T(FH) cells. Moreover, costimulation via ICOS, as well as signaling proteins such as SAP constitute required elements of the regulatory network that modulates T(FH) functions. T(FH) dysregulation has been implicated in the development of autoimmune pathology, such as SLE. Indeed, the Sanroque mice associated to the mutation of Roquin, a ubiquitin ligase, essential for the regulation of ICOS and germinal center responses, constitutes a model that shares features with human SLE. Recently, the expansion of "circulating T(FH) cells" (CD4(+)CXCR5(+)ICOS(high)PD1(high)) has been described for a subset of SLE patients that share T(FH) dependent features of disease with Sanroque mice, such as glomerulonephritis and cytopenias., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Transjugular intrahepatic portosystemic shunt (TIPS) is a safe and effective procedure for the treatment of complications of liver cirrhosis, such as refractory ascites, hepatic hydrothorax and refractory variceal bleeding. The aim of this paper is to describe a rare case of liver failure after a TIPS procedure. A 38-year-old diabetic male with Child-Pugh C liver cirrhosis due to chronic hepatitis C infection who had developed refractory ascites was scheduled for a TIPS procedure. Within 24 h following TIPS placement, the patient developed distributive shock, jaundice, persistentgrade 3 hepatic encephalopathy, severe coagulopathy and acute renal failure. He was treated with lactulose enemas, broad-spectrum antibiotics and blood-derived products. Laboratory data revealed a 100-fold increase in aminotransferases and a non-enhanced computed tomography showed an irregular hypodense area in the right posterior segment of the liver. Despite being initially being in a stable condition, the patient developed progressive liver failure and died 2 mo later. Hepatic infarction is an uncommon phenomenon after a TIPS procedure; however, it can greatly complicate the course of a disease in a patient with an already compromised liver function.

Early Growth Response (EGR) zinc finger transcription factors are induced under diverse mitogenic signals on different cell types such as lymphocytes. Their genetic expression does not require de novo protein synthesis, which suggests its role as immediate response mediators between cell surface receptor signaling and gene expression regulation. EGR factors are involved in modulating the immune response, by means of the induction of differentiation of lymphocyte precursors, activation of T and B cells, as well as their involvement in central and peripheral tolerance. The maturation state, particularly for B cells, and signaling through the T or B cell receptors seems to be quite relevant for the induction of the expression of these transcription factors. EGR-1 functions as a positive regulatory factor for B and T cells mediated by transcriptional regulation of key cytokines and costimulatory molecules, and its interaction with NFAT. On the opposite, EGR-2 and 3 act as negative regulators involved in anergy induction and apoptosis. EGR-2 and 3 deficiency has been related to the development of lupus like disease in murine models. The deficiency of these transcription factors has been associated to deficient Cbl-b expression, a resistant to anergy phenotype, and expansion of effector and activated T cells., (Copyright 2009 Elsevier B.V. All rights reserved.)

Coronary artery dilatations-aneurysms and ectasia-are an uncommon and frequently unrecognized incidental finding in patients with coronary artery disease. Aneurysms and ectasia are associated with a vast group of disorders, and the evaluation and characterization of coronary aneurysms and ectasia represent a great diagnostic task with clinical and therapeutic implications. The underlying etiology is variable and includes degenerative, congenital, inflammatory, infectious, toxic, and traumatic causes. Unlike aneurysms, ectasia is more frequently seen in association with atherosclerosis or as a compensatory mechanism in those cases in which a proximal stenosis is noted in the opposite coronary artery; ectasia is also seen in some coronary artery anomalies, such as anomalous origin from the pulmonary artery, or as a result of a high-flow state, as seen in coronary artery fistulas. The diagnostic approach depends on the clinical scenario, and nowadays, noninvasive evaluation with multidetector computed tomography is possible. Imaging assessment should include evaluation of (a) the distribution, (b) maximal diameter, (c) presence or absence of intraluminal thrombi, (d) number, (e) extension, and (f) associated complications such as myocardial infarction. This article presents an overview of the definition, classification, etiology, clinical manifestations, and potential complications of coronary artery aneurysms and ectasia.

IL-2 plays a key role in setting the balance between immunity and tolerance. This cytokine has a dual role as the regulator of the two main phases of the immune response (proliferative and suppressive). Likewise, activation induced cell death and the induction and maintenance of regulatory T cells are the tolerance mechanisms regulated by IL-2, which convey the link between IL-2 abnormalities and the development of autoimmune disorders, such as systemic lupus erythematosus (SLE). Particularly, in SLE murine models and in humans, deficiency in IL-2 synthesis and activity has been proven. Diverse signaling pathways abnormalities (TCR, NF-kappaBeta, NF-AT) have been involved in the IL-2 transcriptional dysregulation displayed by T cells from SLE patients, and its functional relevance as part of the physiopathogenic scheme has been shown. Aberrant expression and activity of multiple IL-2 transcriptional factors, such as c-fos, and predominantly, CREM and CREB have been involved in this immune dysregulation. Diverse alterations in signaling kinases and phosphatases (PKA, PP2A, CAMKIV) and the modulation by epigenetic mechanisms have been related to the altered CREM/pCREB index. The synergic effect of multiple abnormalities in the transcriptional factors previously mentioned has been shown to be of functional relevance in lupus.

The ubiquitination system comprises a highly specific and regulated post-translational mechanism by which the immune response can be modulated, setting the balance between immunity and tolerance. Proteolysis dependent and independent mechanisms have been implicated. Particularly, the role of ubiquitin ligases as modulators of central and peripheral tolerance has brought attention to this system as one of the key elements of a complex regulatory network designed to maintain an active surveillance system. Cbl-b, GRAIL and Itch are the main E3 ligases, considered as negative regulators of the immune response as part of the genetic program induced by the calcium/calcineurin pathway. Other key signaling pathways for the immune response, such as the NF-kappaB and TGF-beta signaling are prone to be modulated by these ubiquitin ligases. Diverse mechanisms have been implicated in the development of anergy associated to E3 ligases, among these, the setting for TCR responsiveness and repression of cytokine transcription are best well characterized. Also, a role as inductors of regulatory T cells has been evidenced for Cbl-b and GRAIL. The defective expression of some of these E3 ligases has been related to the development of autoimmune disease, in experimental murine and human models, remarking its possible pathogenic role.