title: Superior Cervical Ganglia Neurons Induce Foxp3+ Regulatory T Cells via Calcitonin Gene-Related Peptide.
abstract: The nervous and immune systems communicate bidirectionally, utilizing diverse molecular signals including cytokines and neurotransmitters to provide an integrated response to changes in the body's internal and external environment. Although, neuro-immune interactions are becoming better understood under inflammatory circumstances and it has been evidenced that interaction between neurons and T cells results in the conversion of encephalitogenic T cells to T regulatory cells, relatively little is known about the communication between neurons and naïve T cells. Here, we demonstrate that following co-culture of naïve CD4+ T cells with superior cervical ganglion neurons, the percentage of Foxp3 expressing CD4+CD25+ cells significantly increased. This was mediated in part by immune-regulatory cytokines TGF-β and IL-10, as well as the neuropeptide calcitonin gene-related peptide while vasoactive intestinal peptide was shown to play no role in generation of T regulatory cells. Additionally, T cells co-cultured with neurons showed a decrease in the levels of pro-inflammatory cytokine IFN-γ released upon in vitro stimulation. These findings suggest that the generation of Tregs may be promoted by naïve CD4+ T cell: neuron interaction through the release of neuropeptide CGRP.
authors.affiliation: The Brain Body Institute, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Szklany
authors.affiliation: The Brain Body Institute, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Ruiter
authors.affiliation: The Brain Body Institute, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Firoz
authors.initials: F
authors.lastname: Mian
authors.affiliation: The Brain Body Institute, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kunze
authors.affiliation: The Brain Body Institute, McMaster University, Hamilton, Ontario, Canada.|Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Bienenstock
authors.affiliation: The Brain Body Institute, McMaster University, Hamilton, Ontario, Canada.|Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Forsythe
authors.affiliation: The Brain Body Institute, McMaster University, Hamilton, Ontario, Canada.|Department of Medicine, McMaster University, Hamilton, Ontario, Canada.|Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Khalil
authors.initials: K
authors.lastname: Karimi
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D018920:Coculture Techniques; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000494:pharmacology; D008807:Mice, Inbred BALB C; D020932:Nerve Growth Factor / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D017783:Superior Cervical Ganglion / Q000166:cytology*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007376:Interleukin-2; D014660:Vasoactive Intestinal Peptide; D007371:Interferon-gamma; D020932:Nerve Growth Factor; D015740:Calcitonin Gene-Related Peptide