IgG regulates the CD1 expression profile and lipid antigen-presenting function in human dendritic cells via FcgammaRIIa.

Abstract:

:Dendritic cells (DCs) process and present bacterial and endogenous lipid antigens in complex with CD1 molecules to T cells and invariant natural killer T (NKT) cells. However, different types of DCs, such as blood myeloid DCs and skin Langerhans cells, exhibit distinct patterns of CD1a, CD1b, CD1c, and CD1d expression. The regulation of such differences is incompletely understood. Here, we initially observed that monocyte-derived DCs cultured in an immunoglobulin-rich milieu expressed CD1d but not CD1a, CD1b, and CD1c, whereas DCs cultured in the presence of low levels of immunoglobulins had an opposite CD1 profile. Based on this, we tested the possibility that immunoglobulins play a central role in determining these differences. IgG depletion and intravenous immunoglobulin (IVIg) add-in experiments strongly supported a role for IgG in directing the CD1 expression profile. Blocking experiments indicated that this effect was mediated by FcgammaRIIa (CD32a), and quantitative polymerase chain reaction data demonstrated that regulation of the CD1 profile occurred at the gene expression level. Finally, the ability of DCs to activate CD1-restricted NKT cells and T cells was determined by this regulatory effect of IgG. Our data demonstrate an important role for FcgammaRIIa in regulating the CD1 antigen presentation machinery of human DCs.

journal_name

Blood

journal_title

Blood

authors

Smed-Sörensen A,Moll M,Cheng TY,Loré K,Norlin AC,Perbeck L,Moody DB,Spetz AL,Sandberg JK

doi

10.1182/blood-2007-07-099549

subject

Has Abstract

pub_date

2008-05-15 00:00:00

pages

5037-46

issue

10

eissn

0006-4971

issn

1528-0020

pii

blood-2007-07-099549

journal_volume

111

pub_type

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