PI3K is a negative regulator of IgE production.

Abstract:

:The production of IgE, a main player in allergic disorders such as asthma and atopic dermatitis, is strictly regulated and the serum concentrations of IgE are normally kept at a much lower level than other isotypes. We found that mice deficient for the p85alpha regulatory subunit of class IA phosphoinositide 3-kinase (PI3K) produced increasing amounts of serum IgE. Purified p85alpha-/- B cells produced more IgE than wild-type B cells in vitro in response to anti-CD40 mAb and IL-4. PI3K inhibitors wortmannin and IC87114 enhanced IgE production by wild-type B cells stimulated with anti-CD40 mAb and IL-4. Under the same condition, antigen receptor cross-linking induced the expression of inhibitor of differentiation-2 and suppressed the expression of activation-induced cytidine deaminase and class switch recombination (CSR) in a PI3K-dependent manner. IgE production was also suppressed in a concentrated cell culture condition, which was completely reversed by PI3K inhibition. The selective suppression of IgE production by PI3K was also observed at a protein level after CSR. Our results indicate that PI3K negatively regulates IgE production at both CSR and protein levels.

journal_name

Int Immunol

journal_title

International immunology

authors

Doi T,Obayashi K,Kadowaki T,Fujii H,Koyasu S

doi

10.1093/intimm/dxn009

subject

Has Abstract

pub_date

2008-04-01 00:00:00

pages

499-508

issue

4

eissn

0953-8178

issn

1460-2377

pii

dxn009

journal_volume

20

pub_type

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