Cryptocrine Signaling in the Thymus Network and T Cell Education to Neuroendocrine Self-Antigens

peer reviewedBoth during phylogeny and ontogeny the thymus appears as a nodal point between the two major systems of cell-to-cell signaling, the neuroendocrine and immune systems. This review presents the experimental observations which support a dual role in T cell selection played by the thymic repertoire of neuroendocrine polypeptide precursors. Through the mode of cryptocrine intercellular signaling thymic neuroendocrine-related precursors synthesized in thymic epithelial cells have been shown to influence the early steps in T cell differentiation. In addition, thymic neuroendocrine-related polypeptides are a source of self-antigens which are presented by the major histocompatibility system of the thymic epithelium. Preliminary data also suggest that the intrathymic T cell education to neuroendocrine self-antigens is not strictly superimposible to the antigen presentation by dedicated presenting cells. Insulin-like growth factor-II (IGF-II) was identified as one dominant member of the insulin family expressed by thymic epithelial and nurse cells. The intrathymic presentation of IGF-II or IGF-II derived self-antigens is under current investigation. If further confirmed, the central tolerogenic properties of IGF-II could be considered in the elaboration of a strategy for an efficient and safe prevention of insulin-dependent diabetes

Central self-tolerance by thymic presentation of self-antigens and autoimmunity

Before reacting against non-self infectious agents, the immune system is educated to tolerate the host molecular structure (self). The induction of self-tolerance is a multistep process that begins in the thymus during fetal ontogeny (central tolerance) and also involves inactivating mechanisms outside the thymus (peripheral tolerance). The thymus is the primary lymphoid organ implicated in the development of competent and self-tolerant T cells. During ontogeny, T cell progenitors originating from hemopoietic tissues (yolk sac, fetal liver, and then bone marrow) enter the thymus and undergo a program of proliferation, T cell receptor (TCR) gene rearrangement, maturation and selection. Close interactions between thymocytes (pre-T cells) and the thymic cellular environment are crucial both for T cell development and induction of central self-tolerance. Thymic epithelial and stromal cells synthesize polypeptides belonging to various neuroendocrine families. The thymic repertoire of neuroendocrine-related precursors transposes at the molecular level the dual role of the thymus in T cell negative and positive selection. Thymic precursors not only constitute a source of growth peptides for cryptocrine signaling between thymic stromal cells and pre-T cells, but are also processed in a way that leads to the presentation of self-antigens by thymic major histocompatibility complex (MHC) proteins. Thymic neuroendocrine self-antigens often correspond to peptide sequences highly conserved during the evolution of their corresponding family. The thymic presentation of some neuroendocrine self-antigens is not restricted by MHC alleles. Following the presentation of neuroendocrine self-antigens by thymic MHC proteins, the T cell system might be educated to tolerate main hormone families. Recent experiments argue that a defect in the thymic essential tolerogenic function is implicated as an important factor in the pathophysiology of many autoimmune diseases

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วิทยานิพนธ์ (คศ.ม.) -- มหาวิทยาลัยเทคโนโลยีราชมงคลพระนคร, 2560The research on development of pattern of cotton by using weaving technique in type of Mudmee fabric for metrosexual menswear by method of cutting and connecting has the objectives to : 1) develop pattern of cotton by using weaving technique in type of Mudmee fabric; 2) design of metrosexual menswear by using cutting and connecting from developed Mudmee cotton; 3) design the brand and packaging product to increase product value; 4) survey satisfaction of target group. The researcher studied by using Art Nouveau concept and by designing the cotton pattern by using Mudmee weaving technique, numbering three patterns, binding to make pattern, woven to be fabric, in order to make menswear in metrosexual style by using the method of cutting and connecting prototype, consisting of one set of vest, two sets of suits and two sets of overcoats, as well as designing of brand, numbering five types, at the same time The researcher designed packaging product, in five types, using in surveying satisfaction of target group of thirty persons: Designer, Merchandiser, Graphic designer, Visual merchandiser and person having fabric weaving experience, by method of purposive sampling, analyzing data by using statistics, percentage, mean and standard deviation. The study result was found that most respondents were female, aged 36-40 years, single status, most have taste of female gender, having income of 45,001 Baht onwards. The educational level was Bachelor Degree. Respondents previously bought and used products and accessories for clothes from Mudmee cotton. The types selected to buy the most were vests, bags and shawls, respectively. The occasions in wearing the most of all were important festivals, selecting to buy clothes and accessories for clothes from cotton by using Mudmee weaving technique, in each occasion, price 500-1,000 Baht per one piece. Most persons participating in deciding to buy were friends. The sets of clothes for the groups wishing to design in sets of woman clothes. The result of satisfaction analysis of target group towards development of cotton pattern by using Mudmee weaving technique for metrosexual menswear by using cutting and connecting method, it was found that target group had satisfaction in much level ( x= 4.16). The result of satisfaction analysis of target group towards design of metrosexual menswear by using cutting and connecting method, it was found that target group had satisfaction towards the clothes in every type in much level (x= 4.26). The type which had mean of the highest satisfaction in the three first types, including suit in type No.3 (x = 4.31); the second was vest, type No.1 (x= 4.29) and overcoat, type No.4 (x= 4.27). The result of satisfaction analysis towards format of brand and packaging product, it was found that target group had satisfaction in much level, having x= 4.23 and 4.30 respectively.Rajamangala University of Technology Phra Nakho

Neurohypophysial peptides stimulate the phosphorylation of pre-T cell focal adhesion kinases

Thymic oxytocin (OT) behaves as a cryptocrine signal targeted at the outer surface of thymic epithelial cell plasma membrane from where OT is able to interact with neurohypophysial peptide receptors expressed by pre-T cells. Immature T cells bear a receptor of the V1 subtype, while OT receptors are predominantly expressed by cytotoxic CD8+ lymphocytes. In both T cell types, neurohypophysial peptide receptors transduce OT via the phosphoinositide pathway. Protein tyrosine phosphorylation is an early event of T cell activation. Western blots of murine pre-T cells (RL12-NP line) proteins probed with anti-phosphotyrosine (PY-20) revealed a great number of proteins the phosphorylation of which increased either with OT or vasopressin treatment. Two were immunoprecipitated with anti-focal adhesion kinase (FAK) mAb 2A7 and were identified one as p125FAK and the other as a coprecipitating 130-kDa protein. The p125FAK is connected to the Ras/MAPK pathway and is also implicated in TCR/CD3 signalling in T cell. Another protein phosphorylated by OT in RL12-NP was identified as paxillin, a 68-kDa protein localised at focal adhesion sites and associated with p 125FAK. These results indicate that phosphorylation of focal adhesion kinase may be induced in pre-T cell by thymic OT