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      Dynamic Interactions Between the Immune System and the Neuroendocrine System in Health and Disease

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          Abstract

          The immune system and the neuroendocrine system share many common features. Both consist of diverse components consisting of receptors and networks that are widely distributed throughout the body, and both sense and react to external stimuli which, on the one hand control mechanisms of immunity, and on the other hand control and regulate growth, development, and metabolism. It is thus not surprising, therefore, that the immune system and the neuroendocrine system communicate extensively. This article will focus on bi-directional immune-endocrine interactions with particular emphasis on the hormones of the hypothalamus-pituitary-thyroid (HPT) axis. New findings will be discussed demonstrating the direct process through which the immune system-derived thyroid stimulating hormone (TSH) controls thyroid hormone synthesis and bone metamorphosis, particularly in the context of a novel splice variant of TSHβ made by peripheral blood leukocytes (PBL). Also presented are the ways whereby the TSHβ splice variant may be a contributing factor in the development and/or perpetuation of autoimmune thyroid disease (AIT), and how systemic infection may elicit immune-endocrine responses. The relationship between non-HPT hormones, in particular adipose hormones, and immunity is discussed.

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          Most cited references50

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          Adipokines in inflammation and metabolic disease.

          The worldwide epidemic of obesity has brought considerable attention to research aimed at understanding the biology of adipocytes (fat cells) and the events occurring in adipose tissue (fat) and in the bodies of obese individuals. Accumulating evidence indicates that obesity causes chronic low-grade inflammation and that this contributes to systemic metabolic dysfunction that is associated with obesity-linked disorders. Adipose tissue functions as a key endocrine organ by releasing multiple bioactive substances, known as adipose-derived secreted factors or adipokines, that have pro-inflammatory or anti-inflammatory activities. Dysregulated production or secretion of these adipokines owing to adipose tissue dysfunction can contribute to the pathogenesis of obesity-linked complications. In this Review, we focus on the role of adipokines in inflammatory responses and discuss their potential as regulators of metabolic function.
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            Adipocytokines: mediators linking adipose tissue, inflammation and immunity.

            There has been much effort recently to define the role of adipocytokines, which are soluble mediators derived mainly from adipocytes (fat cells), in the interaction between adipose tissue, inflammation and immunity. The adipocytokines adiponectin and leptin have emerged as the most abundant adipocyte products, thereby redefining adipose tissue as a key component not only of the endocrine system, but also of the immune system. Indeed, as we discuss here, several adipocytokines have a central role in the regulation of insulin resistance, as well as many aspects of inflammation and immunity. Other adipocytokines, such as visfatin, have only recently been identified. Understanding this rapidly growing family of mainly adipocyte-derived mediators might be of importance in the development of new therapies for obesity-associated diseases.
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              Inflammatory links between obesity and metabolic disease.

              The obesity epidemic has forced us to evaluate the role of inflammation in the health complications of obesity. This has led to a convergence of the fields of immunology and nutrient physiology and the understanding that they are inextricably linked. The reframing of obesity as an inflammatory condition has had a wide impact on our conceptualization of obesity-associated diseases. In this Review, we highlight the cellular and molecular mechanisms at play in the generation of obesity-induced inflammation. We also emphasize how defining the immune regulation in metabolic tissues has broadened the understanding of the diversity of inflammatory responses.
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                Author and article information

                Contributors
                Journal
                Front Endocrinol (Lausanne)
                Front Endocrinol (Lausanne)
                Front. Endocrinol.
                Frontiers in Endocrinology
                Frontiers Media S.A.
                1664-2392
                22 March 2021
                2021
                : 12
                : 655982
                Affiliations
                [1] Department of Diagnostic Sciences, School of Dentistry, The University of Texas Health Science Center at Houston , Houston, TX, United States
                Author notes

                Edited by: Premendu Prakash Mathur, Pondicherry University, India

                Reviewed by: Luan Wen, Chinese Academy of Sciences (CAS), China; Kenji Ohba, Hamamatsu University School of Medicine, Japan

                *Correspondence: John R. Klein, john.r.klein@ 123456uth.tmc.edu

                This article was submitted to Neuroendocrine Science, a section of the journal Frontiers in Endocrinology

                Article
                10.3389/fendo.2021.655982
                8020567
                33828532
                651a6dc9-d880-4f89-9844-20f596153186
                Copyright © 2021 Klein

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 19 January 2021
                : 05 March 2021
                Page count
                Figures: 3, Tables: 0, Equations: 0, References: 50, Pages: 6, Words: 2056
                Funding
                Funded by: National Institutes of Health 10.13039/100000002
                Award ID: AI135293
                Categories
                Endocrinology
                Review

                Endocrinology & Diabetes
                systemic regulation and adaptation,hashimoto disease,hematopoiesis,thyroid hormones,integrated

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