Immunotherapeutic targets in estrogen deficiency-dependent Sjögren's syndrome-related manifestations

Immunotherapy
Rieko ArakakiYoshio Hayashi

Abstract

Although a number of autoimmune diseases are known to develop in postmenopausal women, the mechanisms by which estrogen deficiency influences autoimmunity remain unclear. Previously, we found that tissue-specific apoptosis in the exocrine glands in estrogen-deficient mice may contribute to the development of autoimmune exocrinopathy. We found that RbAp48 overexpression induces p53-mediated apoptosis in the exocrine glands depending on estrogen deficiency. RbAp48-inducible transfectants result in rapid apoptosis with p53 phosphorylation (Ser9), and alpha-fodrin cleavage. Indeed, transgenic expression of the RbAp48 gene induced apoptosis in the exocrine glands, resulting in the development of autoimmune exocrinopathy resembling Sjögren's syndrome (SS). CD4(+) T-cell-mediated autoimmune lesions were aggravated with age, in association with production of autoantibodies against SS-A, SS-B and alpha-fodrin. These findings demonstrated that estrogen deficiency initiates tissue-specific apoptosis in the exocrine gland cells through RbAp48 overexpression and exerts a possible gender-based risk of autoimmune exocrinopathy in postmenopausal women. Thus, these data indicate RbAp48 to be a novel immunotherapeutic target for preventing epith...Continue Reading

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Methods Mentioned

BETA
transgenic
PCR
confocal microscopy

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Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.

Apoptosis

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