Vitamin D3 attenuates Th2 responses to Aspergillus fumigatus [mold] mounted by C

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Vitamin D3 attenuates Th2 responses to Aspergillus fumigatus [mold]

mounted by CD4+ T cells from cystic fibrosis patients with allergic

bronchopulmonary aspergillosis – Source: The Journal of Clinical

Investigation,

by L Kreindler, Chad Steele, Kay J Kolls, et al.

_http://www.prohealth.com/library/showarticle.cfm?libid=15556_

(http://www.prohealth.com/library/showarticle.cfm?libid=15556)

[Note: to read the full text of this article free, click here

_http://www.jci.org/articles/view/42388_

(http://www.jci.org/articles/view/42388) .]

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% to 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.

Source: The Journal of Clinical Investigation, Aug 16, 2010, PMID:

20714107, by Kreindler JL, Steele C, Nguyen N, Chan YR, Pilewski JM, Alcorn JF,

Vyas YM, Aujla SJ, Finelli P, Blanchard M, Zeigler SF, Logar A, Hartigan E,

Kurs-Lasky M, Rockette H, Ray A, Kolls JK. Children’s Hospital of

Pittsburgh; Graduate School of Public Health and Division of Pulmonary, Allergy

and

Critical Care Medicine, University of Pittsburgh, Pennsylvania; University

of Alabama at Birmingham; Louisiana State University Health Sciences Center,

New Orleans; Benaroya Research Institute at Virginia Mason, Seattle,

Washington, USA. [Email:

_jkolls@..._ (mailto:jkolls@...) ]