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      The role of sex hormones in women with multiple sclerosis: From puberty to assisted reproductive techniques

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      Frontiers in Neuroendocrinology
      Elsevier BV

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          The X-files in immunity: sex-based differences predispose immune responses

          Sex-based differences in immune responses can influence the susceptibility to autoimmune and infectious diseases and the efficacy of therapeutic drugs. In this Perspective, Eleanor Fish discusses factors, such as X-linked genes, hormones and societal context, that underlie disparate immune responses in men and women.
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            NK cell CD16 surface expression and function is regulated by a disintegrin and metalloprotease-17 (ADAM17).

            The Fc receptor CD16 is present on essentially all CD56(dim) peripheral blood natural killer (NK) cells. Upon recognition of antibody-coated cells it delivers a potent signal to NK cells, which eliminate targets through direct killing and cytokine production. Here we investigated the regulation of CD16 surface expression after NK cell activation. Cytokine activation and target cell stimulation led to marked decreases in CD16 expression. Activation of CD56(dim) NK cells by cross-linking CD16 with antibodies resulted in a loss of CD16 and CD62L, which correlated with increased interferon-γ production. A disintegrin and metalloprotease-17 (ADAM17) is shown to be expressed by NK cells, and its selective inhibition abrogated CD16 and CD62L shedding, and led to enhanced interferon-γ production, especially when triggering was delivered through CD16. Fc-induced production of cytokines by NK cells exposed to rituximab-coated B cell targets was also enhanced by ADAM17 inhibition. This supports an important role for targeting ADAM17 to prevent CD16 shedding and improve the efficacy of therapeutic antibodies. Our findings demonstrate that over-activation of ADAM17 in NK cells may be detrimental to their effector functions by down-regulating surface expression of CD16 and CD62L.
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              Gender differences in autoimmune disease.

              Autoimmune diseases are a range of diseases in which the immune response to self-antigens results in damage or dysfunction of tissues. Autoimmune diseases can be systemic or can affect specific organs or body systems. For most autoimmune diseases there is a clear sex difference in prevalence, whereby females are generally more frequently affected than males. In this review, we consider gender differences in systemic and organ-specific autoimmune diseases, and we summarize human data that outlines the prevalence of common autoimmune diseases specific to adult males and females in countries commonly surveyed. We discuss possible mechanisms for sex specific differences including gender differences in immune response and organ vulnerability, reproductive capacity including pregnancy, sex hormones, genetic predisposition, parental inheritance, and epigenetics. Evidence demonstrates that gender has a significant influence on the development of autoimmune disease. Thus, considerations of gender should be at the forefront of all studies that attempt to define mechanisms that underpin autoimmune disease. Copyright © 2014. Published by Elsevier Inc.
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                Author and article information

                Journal
                Frontiers in Neuroendocrinology
                Frontiers in Neuroendocrinology
                Elsevier BV
                00913022
                January 2021
                January 2021
                : 60
                : 100889
                Article
                10.1016/j.yfrne.2020.100889
                33189769
                edd02dce-b5a5-429c-a597-85037efc7f94
                © 2021

                https://www.elsevier.com/tdm/userlicense/1.0/

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