enhances Archives - World Asthma Foundation

TIGIT Enhances Antigen-Specific Th2 Recall Responses and Allergic Disease.

J Immunol. 2016 Mar 25;

Authors: Kourepini E, Paschalidis N, Simoes DC, Aggelakopoulou M, Grogan JL, Panoutsakopoulou V

Abstract
T cell Ig and ITIM domain receptor (TIGIT), expressed on T, NK, and regulatory T cells, is known as an inhibitory molecule that limits autoimmunity, antiviral and antitumor immunity. In this report, we demonstrate that TIGIT enhances Th2 immunity. TIGIT expression was upregulated in activated Th2 cells from mice with experimental allergic disease and in Th2 polarization cultures. In addition, its high-affinity ligand CD155 was upregulated in mediastinal lymph node dendritic cells from allergic mice. In an in vitro setting, we observed thatTigitexpression in Th2 cells and its interaction with CD155 expressed in dendritic cells were important during the development of Th2 responses. In addition, blockade of TIGIT inhibited Th2, but had no effect on either Th1 or Th17 polarization. In vivo blockade of TIGIT suppressed hallmarks of allergic airway disease, such as lung eosinophilia, goblet cell hyperplasia, Ag-specific Th2 responses, and IgE production, and reduced numbers of T follicular helper and effector Th2 cells. Thus, TIGIT is critical for Th2 immunity and can be used as a therapeutic target, especially in light of recent findings showing TIGIT locus hypomethylation in T cells from pediatric patients with allergic asthma.

PMID: 27016609 [PubMed – as supplied by publisher]

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IL-13 exposure enhances vitamin D-mediated expression of the human cathelicidin antimicrobial peptide-hCAP18/LL-37 in bronchial epithelial cells.

Infect Immun. 2012 Oct 8;

Authors: Schrumpf JA, van Sterkenburg MA, Verhoosel RM, Zuyderduyn S, Hiemstra PS

Abstract
Vitamin D is an important regulator of the expression of antimicrobial peptides, and vitamin D deficiency is associated with respiratory infections. Regulating expression of antimicrobial peptides such as the human cathelicidin antimicrobial peptide (hCAP)18/LL-37 by vitamin D in bronchial epithelial cells requires local conversion of 25(OH)vitaminD(3) (25D(3)) into its bioactive metabolite 1,25(OH)(2)vitaminD(3) (1,25D(3)) by CYP27B1. Low circulating vitamin D-levels in childhood asthma are associated with more severe exacerbations, which are often associated with infections. Atopic asthma is accompanied by Th2 driven inflammation mediated by cytokines such as IL-4 and IL-13, and the effect of these cytokines on vitamin D metabolism and hCAP-18/LL-37 expression is unknown. Therefore we investigated this in well-differentiated bronchial epithelial cells. To this end, cells were treated with IL-13 with and without 25D(3) and expression of hCAP18/LL-37, CYP27B1, the 1,25D(3) inactivating enzyme CYP24A1, and vitamin D receptor was assessed by quantitative PCR. We show that IL-13 enhances the ability of 25D(3) to increase expression of hCAP18/LL-37 and CYP24A1. In addition, exposure to IL-13 resulted in increased CYP27B1 expression, whereas VDR expression was not significantly affected. The enhancing effect of IL-13 on 25D(3)-mediated expression of hCAP18/LL-37 was further confirmed using SDS-PAGE Western Blot and immunofluorescence staining. In conclusion, we demonstrate that IL-13 induces vitamin D(-)dependent hCAP18/LL-37 expression, most likely by increasing CYP27B1. These data suggest that Th2 cytokines regulate the vitamin D metabolic pathway in bronchial epithelial cells.

PMID: 23045480 [PubMed – as supplied by publisher]

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