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Publication : Double negative T cells mediate Lag3-dependent antigen-specific protection in allergic asthma.

First Author  Tian D Year  2019
Journal  Nat Commun Volume  10
Issue  1 Pages  4246
PubMed ID  31534137 Mgi Jnum  J:279374
Mgi Id  MGI:6362313 Doi  10.1038/s41467-019-12243-0
Citation  Tian D, et al. (2019) Double negative T cells mediate Lag3-dependent antigen-specific protection in allergic asthma. Nat Commun 10(1):4246
abstractText  Allergic asthma is an inflammatory disorder of the airway without satisfactory traditional therapies capable of controlling the underlying pathology. New approaches that can overcome the detrimental effects of immune dysregulation are thus desirable. Here we adoptively transfer ovalbumin (OVA) peptide-primed CD4(-)CD8(-) double negative T (DNT) cells intravenously into a mouse model of OVA-induced allergic asthma to find that OVA-induced airway hyperresponsiveness, lung inflammation, mucus production and OVA-specific IgG/IgE production are significantly suppressed. The immunosuppressive function of the OVA-specific DNT cells is dependent on the inhibition of CD11b(+) dendritic cell function, T follicular helper cell proliferation, and IL-21 production. Mechanistically, Lag3 contributes to MHC-II antigen recognition and trogocytosis, thereby modulating the antigen-specific immune regulation by DNT cells. The effectiveness of ex vivo-generated allergen-specific DNT cells in alleviating airway inflammation thus supports the potential utilization of DNT cell-based therapy for the treatment of allergic asthma.
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