title: Vitamin D3 attenuates Th2 responses to Aspergillus fumigatus mounted by CD4+ T cells from cystic fibrosis patients with allergic bronchopulmonary aspergillosis.
abstract: Allergic bronchopulmonary aspergillosis (ABPA) is caused by a dominant Th2 immune response to antigens derived from the opportunistic mold Aspergillus, most commonly Aspergillus fumigatus. It occurs in 4%-15% of patients with cystic fibrosis (CF); however, not all patients with CF infected with A. fumigatus develop ABPA. Therefore, we compared cohorts of A. fumigatus-colonized CF patients with and without ABPA to identify factors mediating tolerance versus sensitization. We found that the costimulatory molecule OX40 ligand (OX40L) was critical in driving Th2 responses to A. fumigatus in peripheral CD4+ T cells isolated from patients with ABPA. In contrast, CD4+ T cells from the non-ABPA cohort did not mount enhanced Th2 responses in vitro and contained a higher frequency of TGF-beta-expressing regulatory T cells. Heightened Th2 reactivity in the ABPA cohort correlated with lower mean serum vitamin D levels. Further, in vitro addition of 1,25 OH-vitamin D3 substantially reduced DC expression of OX40L and increased DC expression of TGF-beta. This in vitro treatment also resulted in increased Treg TGF-beta expression and reduced Th2 responses by CD4+ T cells from patients with ABPA. These data provide rationale for a therapeutic trial of vitamin D to prevent or treat ABPA in patients with CF.
authors: Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors: James L
authors: JL
authors: Kreindler
authors: Chad
authors: C
authors: Steele
authors: Nikki
authors: N
authors: Nguyen
authors: Yvonne R
authors: YR
authors: Chan
authors: Joseph M
authors: JM
authors: Pilewski
authors: John F
authors: JF
authors: Alcorn
authors: Yatin M
authors: YM
authors: Vyas
authors: Shean J
authors: SJ
authors: Aujla
authors: Peter
authors: P
authors: Finelli
authors: Megan
authors: M
authors: Blanchard
authors: Steven F
authors: SF
authors: Zeigler
authors: Alison
authors: A
authors: Logar
authors: Elizabeth
authors: E
authors: Hartigan
authors: Marcia
authors: M
authors: Kurs-Lasky
authors: Howard
authors: H
authors: Rockette
authors: Anuradha
authors: A
authors: Ray
authors: Jay K
authors: JK
authors: Kolls
mesh_terms: D000328:Adult; D001229:Aspergillosis, Allergic Bronchopulmonary / Q000276:immunology*; D001230:Aspergillus / Q000276:immunology; D001232:Aspergillus fumigatus / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002762:Cholecalciferol / Q000494:pharmacology*; D003550:Cystic Fibrosis / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D053262:Receptors, OX40 / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology
chemical_list: D053262:Receptors, OX40; C505716:TNFRSF4 protein, human; D016212:Transforming Growth Factor beta; D002762:Cholecalciferol