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The Neuropeptide Alpha-Melanocyte-Stimulating Hormone Is Critically Involved in the Development of Cytotoxic CD8+ T Cells in Mice and Humans.
- Source :
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PLoS ONE . 2010, Vol. 5 Issue 2, p1-12. 12p. 1 Chart, 7 Graphs. - Publication Year :
- 2010
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Abstract
- Background: The neuropeptide alpha-melanocyte-stimulating hormone is well known as a mediator of skin pigmentation. More recently, it has been shown that alpha-melanocyte-stimulating hormone also plays pivotal roles in energy homeostasis, sexual function, and inflammation or immunomodulation. Alpha-melanocyte-stimulating hormone exerts its antiinflammatory and immunomodulatory effects by binding to the melanocortin-1 receptor, and since T cells are important effectors during immune responses, we investigated the effects of alpha-melanocyte-stimulating hormone on T cell function. Methodology/Principal Findings: T cells were treated with alpha-melanocyte-stimulating hormone, and subsequently, their phenotype and function was analyzed in a contact allergy as well as a melanoma model. Furthermore, the relevance of alpha-melanocyte-stimulating hormone-mediated signaling for the induction of cytotoxicity was assessed in CD8+ T cells from melanoma patients with functional and nonfunctional melanocortin-1 receptors. Here we demonstrate that the melanocortin-1 receptor is expressed by murine as well as human CD8+ T cells, and we furthermore show that alpha-melanocyte-stimulating hormone/melanocortin-1 receptor-mediated signaling is critical for the induction of cytotoxicity in human and murine CD8+ T cells. Upon adoptive transfer, alpha-melanocyte-stimulating hormone-treated murine CD8+ T cells significantly reduced contact allergy responses in recipient mice. Additionally, the presented data indicate that alpha-melanocyte-stimulating hormone via signaling through a functional melanocortin-1 receptor augmented antitumoral immunity by up-regulating the expression of cytotoxic genes and enhancing the cytolytic activity in tumor-specific CD8+ T cells. Conclusions/Significance: Together, these results point to an important role of alpha-melanocyte-stimulating hormone in MHC class I-restricted cytotoxicity. Therefore, treatment of contact allergies or skin cancer with alpha-melanocyte-stimulating hormone or other more stable agonists of melanocortin-1 receptor might ameliorate disease or improve antitumoral immune responses. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 5
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- PLoS ONE
- Publication Type :
- Academic Journal
- Accession number :
- 56550566
- Full Text :
- https://doi.org/10.1371/journal.pone.0008958