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      Sex differences in Sjögren’s syndrome: a comprehensive review of immune mechanisms

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          Abstract

          Autoimmune diseases (ADs) are estimated to affect between 5 and 8 % of the US population, and approximately 80 % of these patients are women. Sjögren’s syndrome (SS) is an AD that occurs predominately in women over men (16:1). The hallmark characteristic of SS is diminished secretory production from the primary exocrine gland and the lacrimal or salivary glands resulting in symptoms of dry eye and mouth. The disease is believed to be mediated by an inflammatory and autoantibody response directed against salivary and lacrimal gland tissues. This review will examine the literature on sex differences in the immune response of patients and animal models of Sjögren’s syndrome in order to gain a better understanding of disease pathogenesis.

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          The complex role of estrogens in inflammation.

          There is still an unresolved paradox with respect to the immunomodulating role of estrogens. On one side, we recognize inhibition of bone resorption and suppression of inflammation in several animal models of chronic inflammatory diseases. On the other hand, we realize the immunosupportive role of estrogens in trauma/sepsis and the proinflammatory effects in some chronic autoimmune diseases in humans. This review examines possible causes for this paradox. This review delineates how the effects of estrogens are dependent on criteria such as: 1) the immune stimulus (foreign antigens or autoantigens) and subsequent antigen-specific immune responses (e.g., T cell inhibited by estrogens vs. activation of B cell); 2) the cell types involved during different phases of the disease; 3) the target organ with its specific microenvironment; 4) timing of 17beta-estradiol administration in relation to the disease course (and the reproductive status of a woman); 5) the concentration of estrogens; 6) the variability in expression of estrogen receptor alpha and beta depending on the microenvironment and the cell type; and 7) intracellular metabolism of estrogens leading to important biologically active metabolites with quite different anti- and proinflammatory function. Also mentioned are systemic supersystems such as the hypothalamic-pituitary-adrenal axis, the sensory nervous system, and the sympathetic nervous system and how they are influenced by estrogens. This review reinforces the concept that estrogens have antiinflammatory but also proinflammatory roles depending on above-mentioned criteria. It also explains that a uniform concept as to the action of estrogens cannot be found for all inflammatory diseases due to the enormous variable responses of immune and repair systems.
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            Sex differences in autoimmune disease.

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              Understanding immunosenescence to improve responses to vaccines.

              In the older adult, the benefits of vaccination to prevent infectious disease are limited, mainly because of the adaptive immune system's inability to generate protective immunity. The age-dependent decrease in immunological competence, often referred to as 'immunosenescence', results from the progressive deterioration of innate and adaptive immune responses. Most insights into mechanisms of immunological aging have been derived from studies of mouse models. In this Review, we explore how well such models are applicable to understanding the aging process throughout the 80-100 years of human life and discuss recent advances in identifying and characterizing the mechanisms that underlie age-associated defective adaptive immunity in humans.
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                Author and article information

                Contributors
                jessica.brandt@duke.edu
                roberta.priori63@gmail.com
                guido.valesini@uniroma1.it
                +1 904-953-6740 , Fairweather.DeLisa@mayo.edu
                Journal
                Biol Sex Differ
                Biol Sex Differ
                Biology of Sex Differences
                BioMed Central (London )
                2042-6410
                3 November 2015
                3 November 2015
                2015
                : 6
                : 19
                Affiliations
                [ ]Department of Environmental Health Sciences, Johns Hopkins University, Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205 USA
                [ ]Reumatologia, Dipartimento di Medicina Interna e Specialita Mediche, Sapienza Universita di Roma, 00161 Rome, Italy
                [ ]Department of Cardiovascular Diseases, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224 USA
                Article
                37
                10.1186/s13293-015-0037-7
                4630965
                26535108
                36fb11e5-9691-4d10-924c-f8644a37f2ea
                © Brandt et al. 2015

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 3 June 2015
                : 17 September 2015
                Categories
                Review
                Custom metadata
                © The Author(s) 2015

                Human biology
                sjögren’s syndrome,sex differences,autoimmune disease,inflammation,autoantibodies,lymphoma

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