IL-27 renders DC immunosuppressive by induction of B7-H1.

Abstract:

:IL-27, an IL-12 family member, was initially described as a proinflammatory cytokine. Nevertheless, it also poses anti-inflammatory activity, being involved in suppressing development of TH-17 cells as well as in the induction of inhibitory Tr1 cells. Recent data obtained in mice suggest that it can down-modulate the function of APCs. However, until now, nothing was known about the influence of IL-27 on human DCs. We investigated the effect of IL-27 on in vitro human MoDCs and on ex vivo blood DCs. Our results show that treatment of mDCs with IL-27 led to specific up-regulation of surface expression of several molecules, including B7-H1, in the absence of general DC maturation. Moreover, we demonstrated that IL-27-treated DCs exhibit a reduced capacity to stimulate proliferation and cytokine production of allogeneic T cells as compared with control DCs. Decisively, we identified B7-H1 as a crucial molecule, responsible for suppressive effects of "IL-27 DC" on T cells. Our data demonstrate for the first time that in addition to the dual role of IL-27 in the modulation of T cell activation and differentiation, human IL-27 modulates an immune response through DCs, i.e., by inducing immunosuppressive B7-H1 molecules and reducing the stimulatory potential of DCs.

journal_name

J Leukoc Biol

authors

Karakhanova S,Bedke T,Enk AH,Mahnke K

doi

10.1189/jlb.1209788

subject

Has Abstract

pub_date

2011-06-01 00:00:00

pages

837-45

issue

6

eissn

0741-5400

issn

1938-3673

pii

jlb.1209788

journal_volume

89

pub_type

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