The Neuroendocrine Thymus: Coexistence of Oxytocin and Neurophysin in the Human Thymus

Geenen, Vincent; Legros, Jean-Jacques; Franchimont, P; Baudrihaye, M.; Defresne, Marie-Paule; Boniver, Jacques

doi:10.1126/science.3961493

Cited by 186 publications

(88 citation statements)

References 21 publications

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“…Unlike the short half-life of exogenous supplements of oxytocin, the plasma elevations seen in the present mice are a consistent and reproducible effect [30], making bacteria or bacterial products a possible therapy for mental health. It remains to be proven whether microbe-induced oxytocin in these murine models originates primarily from the hypothalamus or from other peripheral sources [72][73][74][75][76]. Nonetheless, our results suggest that gut bacteriainduced oxytocin may explain data linking gut microbiome dysbiosis with neuropsychological disorders, including autism [77,78].…”

Section: Discussionmentioning

confidence: 92%

Beneficial Dog Bacteria Up-Regulate Oxytocin and Lower Risk of Obesity

Varian¹,

Levkovich²,

Poutahidis³

et al. 2017

J Prob Health

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AnimalsC57BL/6 wild type (wt), oxytocin-wt (oxt-wt) and oxytocin- AbstractCohabitation with pet dogs imparts diverse health benefits to humans including a slim physique. It is known that neuropeptide hormone oxytocin fundamental in human-canine social bonds regulates appetite and body weight. It was recently shown in mice that consuming Lactobacillus reuteri ATCC 6475 from human breast milk lowers body weight and up-regulates oxytocin levels in blood. Here we test the hypothesis that bacteria from dog saliva may similarly modulate recipient host body weight. We find that a Lactobacillus spp isolate from dog saliva led to lower body weight when fed to C57BL/6 wild type mice. Mice consuming the canineborne L. reuteri also had elevated oxytocin levels in blood plasma, and exhibited body weight in an oxytocin-dependent manner. Interestingly, killed (lysed) canine bacteria were sufficient to achieve the physiological effects. Taken together, these studies provide evidence that dog bacteria modulate oxytocin levels and body weight in recipient mice, and thus may help reduce risk of obesity in individuals cohabitating with pet dogs. knockout (oxt-ko) B6; 129S-Oxttm1Wsy/J mice (purchased initially from Jackson labs; Bar Harbor, ME) were used in three separate experiments (Figure 1). Mice were housed and handled in Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC)-accredited facilities using techniques and diets including Lactobacillus reuteri as specifically approved by Massachusetts Institute of Technology's (MIT) Committee on Animal Care (CAC). Mice were housed under standard 12:12 light cycle conditions with lights on at 7 AM. Mice were fed a standard control chow Purina RMH3000. Beneficial Dog Bacteria Up-Regulate Oxytocin and Lower Risk of ObesityMice were bred in-house to achieve experimental groups. Each experiment included 5-15 animals per group with one or two replications (total N=10-30 mice examined per group) unless otherwise specified. For the initial studies, C57BL/6 wt mice received Lactobacillus reuteri 2546 isolated from dog saliva. To test putative roles for microbeinduced oxytocin in obesity, oxt-ko mice and their oxt-wt littermates entered experiments at eight weeks of age. At the conclusion of the study mice were euthanized with CO 2 overdose, and were examined as described below. Eight pet dogs served as saliva microbe donors as approved by the MIT-CAC. Saliva was collected from these dogs in the morning before feeding using sterile swabs [Puritan Sterile Polyester Tipped applicators Guilford, Me Ref: 25-806 1PD] in 1.5 ml centrifuge tubes (Safeseal Microcentrifuge Tubes, Sorenson Bioscience Inc. Salt Lace City, UT Cat# 16070). Bacteria were purified from dog saliva as described in detail below. PCR of dog saliva for all Lactobacillus speciesSaliva was collected from eight pet dogs and prepared using High Pure PCR Template kit (Roche Diagnostics) was used without changes to the manufacturer's directions to isolate DNA from the canine saliva. DNA was measured using Nan...

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Section: Discussionmentioning

confidence: 92%

Beneficial Dog Bacteria Up-Regulate Oxytocin and Lower Risk of Obesity

Varian¹,

Levkovich²,

Poutahidis³

et al. 2017

J Prob Health

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“…The thymic repertoire of neuroendocrine-related polypeptide precursors has been proposed to recapitulate at the molecular level the dual physiologic role played by the thymus in T-cell development [8][9][10]. With a special regard to the neurohypophysial peptide family, our group as well as others have shown that thymic epithelial and nurse cells (TEC/TNC) synthesize oxytocin (OT) and its precursor-associated protein, OT-neurophysin [11,12]. Thymic OT plays a dual role in T-cell selection.…”

Section: Introductionmentioning

confidence: 99%

Cytokine production by human thymic epithelial cells: control by the immune recognition of the neurohypophysial self-antigen

Martens

Malgrange

Robert

et al. 1996

Regulatory Peptides

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Oxytocin (OT) has been shownto be the dominantpeptideof the neurohypophysial familyexpressedby thymicepithelialand nurse cells (TEC/TNC) invmiousspecies. Thymic OT is not secreted but, after translocation of a hybrid neurophysin/MHC class I protein,is integratedwithinthe plasmamembraneof TEC, thus allowing its presentation to pre-T cells. In order to further demonstrate that thymic OT behaves like a membrane antigen, we assessed the effect of rnAbs to OT on cytokine productions by cultures enriched in human TEC. 75-85% pure TEC cultures were prepared tlom human thymic fragments. Using immunofluorescence and confocal microscopy, ir-OT, ir-interleukin-1~(IL-1P), ir-interleukin-6 (IL-6) and ir-leukemia inhibitory factor (LIF) could be detected in these TEC cultures. ir-OT was restricted to TEC, while some ir-IL-6 and ir-LIF were also seen in occasional fibroblasts. In basal conditions, ir-IL-6 and ir-LIF (but not ir-OT and ir-IL-l@) were detected in the supematants of human TEC cultures. MAbs to OT induced a marked increase of ir-IL-6 and ir-LIF secretion in TEC cultures. No significant effect was observed using mAbs against vasopressin, mouse immunoglobulins, or control ascitic fluid controls. These data show that OT is fully processed and recognized by specific mAbs at the outer surface of TEC plasma membrane. They further support that thymic OT behaves as the self-antigen of the nenrohypophysial family.

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“…This latter can explain why is enhanced thymulin secretion of epithelial cells by it. Pituitary hormones -prolactin, luteinizing and follicle stimulating hormones, corticotropin releasing factor, oxytocin, and vasopressin -are also synthesized by the thymus cells [1,[52][53][54][55], and the cells have pituitary hormone receptors [56].…”

Section: Effect Of Thymic Self-hormones On Non-immune Cells and Functmentioning

confidence: 99%

The Immunoendocrine Thymus as a Pacemaker of Lifespan

Csaba¹

2016

Acta Microbiologica et Immunologica Hungarica

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The thymus develops from an endocrine area of the foregut, and retains the ancient potencies of this region. However, later it is populated by bone marrow originated lymphatic elements and forms a combined organ, which is a central part of the immune system as well as an influential element of the endocrine orchestra. Thymus produces self-hormones (thymulin, thymosin, thymopentin, and thymus humoral factor), which are participating in the regulation of immune cell transformation and selection, and also synthesizes hormones similar to that of the other endocrine glands such as melatonin, neuropeptides, and insulin, which are transported by the immune cells to the sites of requests (packed transport). Thymic (epithelial and immune) cells also have receptors for hormones which regulate them. This combined organ, which is continuously changing from birth to senescence seems to be a pacemaker of life. This function is basically regulated by the selection of self-responsive thymocytes as their complete destruction helps the development (up to puberty) and their gradual release in case of weakened control (after puberty) causes the erosion of cells and intercellular material, named aging. This means that during aging, self-destructive and non-protective immune activities are manifested under the guidance of the involuting thymus, causing the continuous irritation of cells and organs. Possibly the pineal body is the main regulator of the pacemaker, the neonatal removal of which results in atrophy of thymus and wasting disease and its later corrosion causes the insufficiency of thymus. The co-involution of pineal and thymus could determine the aging and the time of death without external intervention; however, external factors can negatively influence both of them.

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The Neuroendocrine Thymus: Coexistence of Oxytocin and Neurophysin in the Human Thymus

Cited by 186 publications

References 21 publications

Beneficial Dog Bacteria Up-Regulate Oxytocin and Lower Risk of Obesity

Beneficial Dog Bacteria Up-Regulate Oxytocin and Lower Risk of Obesity

Cytokine production by human thymic epithelial cells: control by the immune recognition of the neurohypophysial self-antigen

The Immunoendocrine Thymus as a Pacemaker of Lifespan

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