The effect of types I and III interferons on adrenocortical cells and its possible implications for autoimmune Addison's disease

Hellesen, Alexander; Edvardsen, K.S.W.; Breivik, Lars; Husebye, Eystein S.; Bratland, Eirik

doi:10.1111/cei.12291

Cited by 14 publications

(17 citation statements)

References 63 publications

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“…The CXCL10 produced by the adrenal cortex acts as a chemotactic signal for IFN‐γ‐producing CD4 + and CD8 + T cells bearing the chemokine receptor CXCR3. In concordance with this we have demonstrated that 21OH‐specific T cells from AAD patients express high levels of CXCR3 and are able to migrate towards CXCL10‐containing cell culture supernatants from IFN‐γ/poly (I:C)‐stimulated adrenocortical cells . In a genetically predisposed individual infected by a virus able to infect and replicate in the adrenal cortex, TLR‐3 may sense the infection through dsRNA.…”

Section: Pathogenesis Of Autoimmune Addison’s Disease and Implicationsupporting

confidence: 81%

“…For illustrative reasons, CXCL9 is not included in the figure, but may play an accompanying role in the recruitment of autoaggressive T cells in phase 2. [Colour figure can be viewed at wileyonlinelibrary.com] culture supernatants from IFN-γ/poly (I:C)-stimulated adrenocortical cells [104]. In a genetically predisposed individual infected by a virus able to infect and replicate in the adrenal cortex, TLR-3 may sense the infection through dsRNA.…”

Section: Pathogenesis Of Autoimmune Addison's Disease and Implicationmentioning

confidence: 99%

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The potential role for infections in the pathogenesis of autoimmune Addison’s disease

Hellesen

Bratland

2018

Clinical and Experimental Immunology

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Autoimmune Addison's disease (AAD), or primary adrenocortical insufficiency, is a classical organ-specific autoimmune disease with 160 years of history. AAD is remarkably homogeneous with one major dominant self-antigen, the cytochrome P450 21-hydroxylase enzyme, which is targeted by both autoantibodies and autoreactive T cells. Like most autoimmune diseases, AAD is thought to be caused by an unfortunate combination of genetic and environmental factors. While the number of genetic associations with AAD is increasing, almost nothing is known about environmental factors. A major environmental factor commonly proposed for autoimmune diseases, based partly on experimental and clinical data and partly on shared pathways between anti-viral immunity and autoimmunity, is viral infections. However, there are few reports associating viral infections to AAD, and it has proved difficult to establish which immunological processes that could link any viral infection with the initiation or progression of AAD. In this review, we will summarize the current knowledge on the underlying mechanisms of AAD and take a closer look on the potential involvement of viruses.

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Section: Pathogenesis Of Autoimmune Addison’s Disease and Implicationsupporting

confidence: 81%

Section: Pathogenesis Of Autoimmune Addison's Disease and Implicationmentioning

confidence: 99%

The potential role for infections in the pathogenesis of autoimmune Addison’s disease

Hellesen

Bratland

2018

Clinical and Experimental Immunology

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“…Activation of IFNa pathways were related to several autoimmune diseases, such as systemic lupus erythematosus, Addison's disease, etc. [88]. Miscarriage of humans and animals has been associated with higher levels of IFNg, that, on the other hand, is involved in maintaining the decidual layer and vascular remodeling in the uterus [89].…”

Section: Interferon-induced Diseasesmentioning

confidence: 99%

“…Abnormality in IFN-stimulated gene patterns, causing failures in immunotolerance in early childhood were proposed to be contribute to the development of type 1 diabetes and cases of type 1 diabetes were also related to treatments with pegylated IFN and ribavirin for chronic hepatitis C [90]. Cardiovascular complications can be observed in IFN-treated subjects (arrhythmia, myocarditis, reversible hypertension, ischemic heart disease, pericarditis and pericardial effusion, cardiomyopathy) and are generally reversible [88]. Sarcoidosis, a systemic chronic granulomatous disease of unknown cause, is a rare adverse effect from the use of type I IFNa and IFNb, that reflects an exaggerated cellmediated immune response to an unknown persistent antigen, with higher levels of circulating IFNg [91].…”

Section: Interferon-induced Diseasesmentioning

confidence: 99%

Type I IFN family members: Similarity, differences and interaction

Capobianchi

Uleri

Caglioti

et al. 2015

Cytokine & Growth Factor Reviews

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Interferons (IFN) are key cytokines with multifaceted antiviral and cell-modulatory properties. Three distinct types of IFN are recognized (I-III) based on structural features, receptor usage, cellular source and biological activities. The action of IFNs is mediated by a complex, partially overlapping, transcriptional program initiated by the interaction with specific receptors. Genetic diversity, with polymorphisms and mutations, can modulate the extent of IFN responses and the susceptibility to infections. Almost all viruses developed mechanisms to subvert the IFN response, involving both IFN induction and effector mechanisms. Interactions between IFN types may occur, for both antiviral and cell-modulatory effects, in a complex interplay, involving both synergistic and antagonistic effects. Interferon-associated diseases, not related to virus infections may occur, some of them frequently observed in IFN-treated patients. On the whole, IFNs are pleiotropic biologic response modifiers, that, upon activation of thousands genes, induce a broad spectrum of activities, regulating cell cycle, differentiation, plasma membrane molecules, release of mediators, etc., that can be relevant for cell proliferation, innate and adaptive immunity, hematopoiesis, angiogenesis and other body functions.

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“…A number of susceptibility loci for AAD in the innate immune pathways have been discovered including NLRP1 , CLEC16A , VDR , and CYP27B1 (4, 25–27). In addition, experimental data also support the role of innate immunity in the pathophysiology of AAD (28). It is plausible that early priming of immune cells and immune mechanisms induced by exposure to various (seasonally influenced) pathogens can influence disease risk in individuals who carry multiple other susceptibility alleles.…”

Section: Discussionmentioning

confidence: 75%

Impact of Month of Birth on the Risk of Development of Autoimmune Addison’s Disease

Pazderska

Fichna

Mitchell

et al. 2016

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context:The pathogenesis of autoimmune Addison's disease (AAD) is thought to be due to interplay of genetic, immune, and environmental factors. A month-of-birth effect, with increased risk for those born in autumn/winter months, has been described in autoimmune conditions such as type 1 diabetes and autoimmune thyroid disease.Objective:Month-of-birth effect was investigated in 2 independent cohorts of AAD subjects.Design, Setting, and Patients:The monthly distribution of birth in AAD patients was compared with that of the general population using the cosinor test. A total of 415 AAD subjects from the United Kingdom cohort were compared with 8 180 180 United Kingdom births, and 231 AAD subjects from the Polish cohort were compared with 2 421 384 Polish births.Main Outcome Measures:Association between month of birth and the susceptibility to AAD.Results:In the entire cohort of AAD subjects, month-of-birth distribution analysis showed significant periodicity with peak of births in December and trough in May (P = .028). Analysis of the odds ratio distribution based on month of birth in 2 cohorts of patients with AAD versus the general population revealed a December peak and May trough, and January peak and July trough, in the United Kingdom and Polish cohorts, respectively.Conclusion:For the first time, we demonstrate that month of birth exerts an effect on the risk of developing AAD, with excess risk in individuals born in winter months and a protective effect when born in the summer. Exposure to seasonal viral infections in the perinatal period, coupled with vitamin D deficiency, could lead to dysregulation of innate immunity affecting the risk of developing AAD.

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The effect of types I and III interferons on adrenocortical cells and its possible implications for autoimmune Addison's disease

Cited by 14 publications

References 63 publications

The potential role for infections in the pathogenesis of autoimmune Addison’s disease

The potential role for infections in the pathogenesis of autoimmune Addison’s disease

Type I IFN family members: Similarity, differences and interaction

Impact of Month of Birth on the Risk of Development of Autoimmune Addison’s Disease

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