Type 1 cytokines polarize thymocytes during T cell development in adult thymus organ cultures

Whalen, Barbara J.; Marounek, Jan; Mordes, John P.; Rossini, Aldo A.; Greiner, Dale L.

doi:10.1016/s0896-8411(02)00091-4

Cited by 4 publications

(3 citation statements)

References 72 publications

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“…The adult thymic organ culture (ATOC) system has been used to study T cell development ex vivo (17). Co-culture of FoxP3-transduced iPS cells in ATOC for 2 weeks resulted in the generation of CD4 + CD25 + FoxP3 + Treg cells (Fig.…”

Section: Resultsmentioning

confidence: 99%

Programming of Regulatory T Cells from Pluripotent Stem Cells and Prevention of Autoimmunity

Haque

Lei

Xiong

et al. 2012

The Journal of Immunology

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Regulatory T (Treg) cells are being used to treat autoimmunity and prevent organ rejection; however, Treg cell-based therapies have been hampered by the technical limitation in obtaining a high number of functional Treg cells. Here we show how to generate functional Treg cells from induced pluripotent stem (iPS) cells, and to determine the potential role of such cells for Treg-based immunotherapy against autoimmunity in a therapeutic setting. Ligation of a Notch ligand and transduction of the gene of forkhead box P3 (FoxP3) induce iPS cells to differentiate into Treg cells. Expression of FoxP3 and co-culture on Notch ligand-expressing stromal cells augment expression of CD3, TCR, CD4, CD25, and CTLA-4 on iPS cell-differentiated Treg cells, which are able to secrete TGF-β and IL-10 both in vivo and in vitro. Importantly, adoptive transfer of iPS cell-derived Treg cells expressing large amounts of FoxP3 and Bcl-xL significantly suppresses host immune responses and reduces arthritis development within murine models. These data suggest that Notch signaling and FoxP3 regulate the development and function of Treg cells derived from iPS cells. Our results provide a novel approach for generating potentially therapeutic Treg cells for the treatment of autoimmune diseases.

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Section: Resultsmentioning

confidence: 99%

Programming of Regulatory T Cells from Pluripotent Stem Cells and Prevention of Autoimmunity

Haque

Lei

Xiong

et al. 2012

The Journal of Immunology

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“…ing Thymus after Diet-Restriction Treatment Previous studies have reported decreased thymus weight relative to body weight after diet-restriction treatment. 3,18) Diet-restriction treatment for 48 h resulted in approximately 18% reduction in body weight (Fig. 1A).…”

Section: Expression Of Inflammatory Cytokines In the Involut-mentioning

confidence: 99%

Induced Prostanoid Synthesis Regulates the Balance between Th1- and Th2-Producing Inflammatory Cytokines in the Thymus of Diet-Restricted Mice

Razali

Hitomi

Inazumi

et al. 2020

Biological & Pharmaceutical Bulletin

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Multiple external and internal factors have been reported to induce thymic involution. Involution involves dramatic reduction in size and function of the thymus, leading to various immunodeficiency-related disorders. Therefore, clarifying and manipulating molecular mechanisms governing thymic involution are clinically important, although only a few studies have dealt with this issue. In the present study, we investigated the molecular mechanisms underlying thymic involution using a murine acute diet-restriction model. Gene expression analyses indicated that the expression of T helper 1 (Th1)-producing cytokines, namely interferon-γ and interleukin (IL)-2, was down-regulated, while that of Th2-producing IL-5, IL-6, IL-10 and IL-13 was up-regulated, suggesting that acute diet-restriction regulates the polarization of naïve T cells to a Th2-like phenotype during thymic involution. mRNAs for prostanoid biosynthetic enzymes were up-regulated by acute diet-restriction. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyses detected the increased production of prostanoids, particularly prostaglandin D 2 and thromboxane B 2 , a metabolite of thromboxane A 2 , in the diet-restricted thymus. Administration of non-steroidal anti-inflammatory drugs, namely aspirin and etodolac, to inhibit prostanoid synthesis suppressed the biased expression of Th1and Th2-cytokines as well as molecular markers of Th1 and Th2 cells in the diet-restricted thymus, without affecting the reduction of thymus size. In vitro stimulation of thymocytes with phorbol myristate acetate (PMA)/ionomycin confirmed the polarization of thymocytes from diet-restricted mice toward Th2 cells. These results indicated that the induced production of prostanoids during diet-restriction-induced thymic involution is involved in the polarization of naïve T cells in the thymus.

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“…It is also possible that thymocytes may be directed to cytokine synthesis by peripherally produced cytokines by inflammatory cells activated by PM exposure. It was evidenced that type 1 cytokines can polarize thymocyte differentiation in terms of surface markers expression and cytokine production in thymus organ cultures (207). Thus, the alterations in the thymocyte development may result from the changes in the thymic environment caused by complex xenobiotic exposure.…”

Section: Non‐receptor‐mediated Effectsmentioning

confidence: 99%

Xenobiotic‐induced alterations in thymocyte development

Drela

2006

APMIS

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The thymus is a very sensitive target for environmental pollutants, which can affect this organ as well as thymocyte differentiation. A failure in thymocyte development can be due to the exacerbation of apoptosis, arrest of thymocyte maturation, generation of autoreactive T cells, and inhibition or stimulation of the output of recent thymic emigrants to the periphery. Recent data demonstrate that the immune system has the potential to maintain homeostasis under conditions of elevated risk, and the thymus plays a crucial role in this process. Environmental xenobiotics can exert their effects through receptor-mediated interactions or independently on receptor involvement. Under natural conditions organisms are exposed to a variety of xenobiotics. The final effect of such exposure is not related to the action of a single chemical, but to the action of a mixture of chemicals. The toxic effect of environmental xenobiotics on the generation and functions of immune cells may result in suppression or stimulation of the immune response. The most intensive studies have been done on halogenated aromatic hydrocarbons, heavy metals and various chemicals acting as endocrine disrupters. Recently, special interest has focused on the action of air particulate matter.

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Type 1 cytokines polarize thymocytes during T cell development in adult thymus organ cultures

Cited by 4 publications

References 72 publications

Programming of Regulatory T Cells from Pluripotent Stem Cells and Prevention of Autoimmunity

Programming of Regulatory T Cells from Pluripotent Stem Cells and Prevention of Autoimmunity

Induced Prostanoid Synthesis Regulates the Balance between Th1- and Th2-Producing Inflammatory Cytokines in the Thymus of Diet-Restricted Mice

Xenobiotic‐induced alterations in thymocyte development

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