Neuropeptides, by direct interaction with T cells, induce cytokine secretion and break the commitment to a distinct T helper phenotype

Levite, Mia

doi:10.1073/pnas.95.21.12544

Cited by 205 publications

(158 citation statements)

References 34 publications

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“…Our study demonstrates that NPY also plays an important role in the regulation of EAE. It has previously been indicated that NPY modulates various T cell functions in vitro, including T cell adhesion to integrins (30) and cytokine secretion of in vitro established T clones (22,23). Our study could be regarded as the first work to provide evidence that NPY modulates T cell function in vivo and that NPY is involved in the natural regulation of Th1-mediated autoimmunity.…”

Section: Discussionmentioning

confidence: 68%

“…These results suggested a role for NPY in neuroimmune interactions. In support of this hypothesis, two independent studies previously showed that NPY significantly modifies the cytokine profile of T helper clone cells in vitro (22,23). Namely, Levite (23) reported NPY converts the cytokine profile of Th1 clones to a Th0 type in vitro, whereas Kawamura et al (22) showed that NPY inhibits the IFN-␥ production by Th1 clones as well as that of freshly isolated spleen T cells.…”

Section: E Xperimental Autoimmune Encephalomyelitis (Eae)mentioning

confidence: 59%

“…NPY has been demonstrated to alter the cytokine profile of in vitro established Th1 clones toward Th2 directions (22,23). We therefore speculated that the inhibitory action of NPY on EAE might be due to a modulation of the Th1/Th2 balance resulting from a Th2 bias of MOG -reactive T cells.…”

Section: Eae Suppression Is Associated With An Inhibition Of Mog 35-5mentioning

confidence: 99%

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Neuropeptide Y (NPY) Suppresses Experimental Autoimmune Encephalomyelitis: NPY1 Receptor-Specific Inhibition of Autoreactive Th1 Responses In Vivo

Bedoui

Miyake

Lin

et al. 2003

The Journal of Immunology

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Prior studies have revealed that the sympathetic nervous system regulates the clinical and pathological manifestations of experimental autoimmune encephalomyelitis (EAE), an autoimmune disease model mediated by Th1 T cells. Although the regulatory role of catecholamines has been indicated in the previous works, it remained possible that other sympathetic neurotransmitters like neuropeptide Y (NPY) may also be involved in the regulation of EAE. Here we examined the effect of NPY and NPY receptor subtype-specific compounds on EAE, actively induced with myelin oligodendrocyte glycoprotein 35–55 in C57BL/6 mice. Our results revealed that exogenous NPY as well as NPY Y1 receptor agonists significantly inhibited the induction of EAE, whereas a Y5 receptor agonist or a combined treatment of NPY with a Y1 receptor antagonist did not inhibit signs of EAE. These results indicate that the suppression of EAE by NPY is mediated via Y1 receptors. Furthermore, treatment with the Y1 receptor antagonist induced a significantly earlier onset of EAE, indicating a protective role of endogenous NPY in the induction phase of EAE. We also revealed a significant inhibition of myelin oligodendrocyte glycoprotein 35–55-specific Th1 response as well as a Th2 bias of the autoimmune T cells in mice treated with the Y1 receptor agonist. Ex vivo analysis further demonstrated that autoimmune T cells are directly affected by NPY via Y1 receptors. Taken together, we conclude that NPY is a potent immunomodulator involved in the regulation of the Th1-mediated autoimmune disease EAE.

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Section: Discussionmentioning

confidence: 68%

Section: E Xperimental Autoimmune Encephalomyelitis (Eae)mentioning

confidence: 59%

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Neuropeptide Y (NPY) Suppresses Experimental Autoimmune Encephalomyelitis: NPY1 Receptor-Specific Inhibition of Autoreactive Th1 Responses In Vivo

Bedoui

Miyake

Lin

et al. 2003

The Journal of Immunology

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“…Recent reports have also indicated that somatostatin is involved in immunomodulation, such as the regulation of proliferative responses to antigens or mitogens in different types of immune cells, or the balance between Th1 and Th2 patterns of cytokine secretion by CD4 þ T-lymphocytes (17,18). The present report describes the case of a 37-year-old female displaying TSHoma with Graves' disease.…”

Section: Introductionmentioning

confidence: 91%

“…Somatostatin has recently been suggested to be involved in immunomodulation (18,34). As somatostatin is also reportedly able to induce a Th2-like pattern of cytokine secretion in the absence of mitogens (17), the analog octreotide may trigger a shift in Hashimoto's thyroiditis-associated Th1 predominant activation (33) by binding to SSTR2A expressed by infiltrated lymphocytes within the thyroid. We actually verified that titers of TRAb and TSAb are increased after octreotide administration (dashed square, Fig.…”

Section: Discussionmentioning

confidence: 99%

Thyrotropin-producing pituitary adenoma associated with Graves' disease

Koriyama

Nakazaki

Hashiguchi

et al. 2004

European Journal of Endocrinology

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Objectives: The examination of potential associations between Graves' disease and thyrotropin-producing pituitary adenoma (TSHoma) after treatment using octreotide, and of the expression of peroxisome proliferator-activated receptor g (PPARg). Design and methods: A specimen of resected TSHoma tissue from our case was immunohistochemically examined for expression of somatostatin receptor 2A (SSTR2A) and PPARg. Specimens of thyroid tissue from two cases with Hashimoto's thyroiditis were immunohistochemically examined for expression of SSTR2A.

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Dopamine interacts directly with its D3 and D2 receptors on normal human T cells, and activates β1 integrin function

et al. 2001

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Dopamine by itself has not up to now been reported to activate T cell function. We show here that dopamine interacts directly with dopaminergic receptors on normal human T cells and triggers β1 integrin‐mediated T cell adhesion to a major extracellular matrix component, fibronectin (FN). Such adhesion is a characteristic feature of activated T cells, and is critical for trafficking and extravasation of T cells across blood vessels and tissue barriers. Seven dopamine D2/D3 receptor agonists and antagonists were used to identify the receptor subtypes with which dopamine specifically interacts to activate T cells. The D3 dopamine receptor agonist, 7‐hydroxy‐DPAT (DPAT), mimics the effects of dopamine, and the effects of both dopamine and DPAT are blocked by a specific D3 receptor antagonist, U‐maleate. The dopamine receptor agonists bromocriptine and pergolide mimic the direct effect of dopamine on the β1 integrin function, while the dopamine receptor antagonists butaclamol and haloperidol suppress it, suggesting additional signaling via the dopamine D2 receptor subtype. Our study shows, for the first time, that dopamine can directly activate T cells via ist specific receptors and suggests a possible role for dopamine in integrin‐mediated cellular trafficking and extravasation of T cells in the central nervous system and possibly also in the periphery. Finally, we suggest that the reported changes in the D3 and D2 receptor RNA levels in peripheral blood lymphocytes of individuals with schizophrenia, Parkinson's disease, Alzheimer's disease and migraine can serve not only as a ‘passive’ diagnostic marker, but primarily reflect the dynamic functional dopamine‐T cell interactions in these diseases.

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Neuropeptides, by direct interaction with T cells, induce cytokine secretion and break the commitment to a distinct T helper phenotype

Abstract: Searching for nervous system candidates that could directly induce T cell cytokine secretion, I tested four neuropeptides (

Cited by 205 publications

References 34 publications

Neuropeptide Y (NPY) Suppresses Experimental Autoimmune Encephalomyelitis: NPY1 Receptor-Specific Inhibition of Autoreactive Th1 Responses In Vivo

Neuropeptide Y (NPY) Suppresses Experimental Autoimmune Encephalomyelitis: NPY1 Receptor-Specific Inhibition of Autoreactive Th1 Responses In Vivo

Thyrotropin-producing pituitary adenoma associated with Graves' disease

Dopamine interacts directly with its D3 and D2 receptors on normal human T cells, and activates β1 integrin function

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