Autoimmune Disease 2002: An Overview

Autoimmune disease includes a large spectrum of clinically distinct entities that share a common etiology, a misguided, self-directed immune response. Collectively, they are major contributors to morbidity and mortality. Normally, the body utilizes a number of strategies to avoid the pathologic consequences of autoimmune reactions, but these defenses may fail for a combination of hereditary and environmental factors. Infection has long been regarded as a common environmental trigger of autoimmune disease. Our laboratory has developed a mouse model of myocarditis induced by Coxsackievirus B3 infection and demonstrated some of the steps involved in the transition from an infection to an autoimmune disease. Such basic studies may suggest improved treatment or preventive measures for this group of diseases

Nasal administration of cardiac myosin suppresses autoimmune myocarditis in mice

AbstractOBJECTIVESThis study was designed to examine whether myocarditis induced in a mouse model can be effectively suppressed by nasal administration of cardiac myosin (CM).BACKGROUNDMyocarditis in humans often follows viral infection and is accompanied by evidence of an autoimmune response to CM. Treatment has been hampered by the fact that measures undertaken to reduce the autoimmune response often enhance the viral infection. Delivery of antigen via nasal route has been shown to induce antigen-specific tolerance and suppress certain autoimmune diseases in animal models.METHODSMyocarditis was induced in A/J mice by two subcutaneous injections of CM emulsified in complete Freund’s adjuvant. Nasal instillation of CM (200 μg/mouse) or vehicle buffer was carried out three days before the first subcutaneous injection (day −3). The effect of nasal instillation of CM on cardiac histopathology, cytokine production by splenocytes, and antibody response was examined three weeks after the first subcutaneous injection (day 21).RESULTSNasal administration of CM effectively reduced the severity of myocarditis. Consistent with the histological findings, the levels of interleukin-2 (IL-2), tumor necrosis factor-α, and IL-1β produced by splenocytes in response to CM were significantly decreased. In addition, the serum levels of IgE and IgG1 anti-myosin antibodies were suppressed. However, the levels of transforming growth factor-β (TGF-β) and CM-specific IgA antibodies were not affected.CONCLUSIONSTaken together, our results do not support active suppression through upregulation of TGF-β, IL-4, and IL-10 as a mechanism of tolerance, but favor anergy or deletion of both Th1 and Th2 autoreactive T cells

Invariant NKT Cell Lines Derived from the NOD·H2h4 Mouse Enhance Autoimmune Thyroiditis

To study the role of invariant Natural Killer T cell ( iNKT) cells in autoimmune thyroiditis, we derived two iNKT cell lines from the spleens of NOD· H2h4 mice, a strain that develops spontaneous autoimmune thyroiditis exacerbated by excess dietary iodine. The two lines were CD1d-restricted and expressed CD4+, DX5+, and the Vα4Jα281 gene segment, of the T-cell receptor α locus. Upon stimulation with α-galactosyl-ceramide (α-GalCer), both lines rapidly produced IL-2, IL-4, IFN-γ, IL-10, and TNF-α. Strikingly, a similar cytokine response was also induced by thyroglobulin, one of the most abundant protein in the thyroid gland and a major autoantigen in human autoimmune thyroiditis. Transfer of the iNKT cell lines to syngeneic hosts enhanced autoimmune thyroiditis. Intraperitoneal injections of α-GalCer in iodine primed mice also induced thyroid disease. This paper reports for the first time that iNKT cells respond to thyroglobulin and enhance autoimmune thyroiditis in iodine fed NOD·H2h4 mice

Women and Autoimmune Diseases1

Recent evidence indicates that sex hormones may exacerbate autoimmune diseases, particularly in women, by increasing the adjuvant effect of infections

Immunoproteasome Overexpression Underlies the Pathogenesis of Thyroid Oncocytes and Primary Hypothyroidism: Studies in Humans and Mice

BACKGROUND:Oncocytes of the thyroid gland (Hürthle cells) are found in tumors and autoimmune diseases. They have a unique appearance characterized by abundant granular eosinophilic cytoplasm and hyperchromatic nucleus. Their pathogenesis has remained, thus far, unknown. METHODOLOGY/PRINCIPAL FINDINGS:Using transgenic mice chronically expressing IFNgamma in thyroid gland, we showed changes in the thyroid follicular epithelium reminiscent of the human oncocyte. Transcriptome analysis comparing transgenic to wild type thyrocytes revealed increased levels of immunoproteasome subunits like LMP2 in transgenics, suggesting an important role of the immunoproteasome in oncocyte pathogenesis. Pharmacologic blockade of the proteasome, in fact, ameliorated the oncocytic phenotype. Genetic deletion of LMP2 subunit prevented the development of the oncocytic phenotype and primary hypothyroidism. LMP2 was also found expressed in oncocytes from patients with Hashimoto thyroiditis and Hürthle cell tumors. CONCLUSIONS/SIGNIFICANCE:In summary, we report that oncocytes are the result of an increased immunoproteasome expression secondary to a chronic inflammatory milieu, and suggest LMP2 as a novel therapeutic target for the treatment of oncocytic lesions and autoimmune hypothyroidism

Natural Killer Cells Limit Cardiac Inflammation and Fibrosis by Halting Eosinophil Infiltration

Myocarditis is a leading cause of sudden cardiac failure in young adults. Natural killer (NK) cells, a subset of the innate lymphoid cell compartment, are protective in viral myocarditis. Herein, we demonstrated that these protective qualities extend to suppressing autoimmune inflammation. Experimental autoimmune myocarditis (EAM) was initiated in BALB/c mice by immunization with myocarditogenic peptide. During EAM, activated cardiac NK cells secreted interferon γ, perforin, and granzyme B, and expressed CD69, tumor necrosis factor–related apoptosis-inducing ligand treatment, and CD27 on their cell surfaces. The depletion of NK cells during EAM with anti-asialo GM1 antibody significantly increased myocarditis severity, and was accompanied by elevated fibrosis and a 10-fold increase in the percentage of cardiac-infiltrating eosinophils. The resultant influx of eosinophils to the heart was directly responsible for the increased disease severity in the absence of NK cells, because treatment with polyclonal antibody asialogangloside GM-1 did not augment myocarditis severity in eosinophil-deficient ΔdoubleGATA1 mice. We demonstrate that NK cells limit eosinophilic infiltration both indirectly, through altering eosinophil-related chemokine production by cardiac fibroblasts, and directly, by inducing eosinophil apoptosis in vitro. Altogether, we define a new pathway of eosinophilic regulation through interactions with NK cells

ONLINE MULTIMEDIA SCREEN TIME AND LEVEL OF HAPPINESS OF THE COLLEGE STUDENTS

Online multimedia is very popular in today’s generation. Many people are using different online multimedia platforms as a means to enjoy, study, and connect with other people around the world. This study sought to determine the online multimedia screen time and the level of happiness of the college students of Notre Dame of Midsayap College as well as the relationship between these two variables. The researchers used descriptive- correlational research design and purposive sampling technique in gathering data through a survey questionnaire administered to 50 respondents who are active users of different online multimedia. The findings of the study revealed that online multimedia screen time and level of happiness have a significant relationship. Furthermore, contrary to the findings of previous studies, this study suggests that if online multimedia screen time is increased, students’ level of happiness also increases.  Article visualizations