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Suppression of antigen-specific adaptive immunity by IL-37 via induction of
tolerogenic dendritic cells
#MMPMID25294929
Luo Y
; Cai X
; Liu S
; Wang S
; Nold-Petry CA
; Nold MF
; Bufler P
; Norris D
; Dinarello CA
; Fujita M
Proc Natl Acad Sci U S A
2014[Oct]; 111
(42
): 15178-83
PMID25294929
show ga
IL-1 family member IL-37 limits innate inflammation in models of colitis and
LPS-induced shock, but a role in adaptive immunity remains unknown. Here, we
studied mice expressing human IL-37b isoform (IL-37tg) subjected to skin contact
hypersensitivity (CHS) to dinitrofluorobenzene. CHS challenge to the hapten was
significantly decreased in IL-37tg mice compared with wild-type (WT) mice (-61%;
P < 0.001 at 48 h). Skin dendritic cells (DCs) were present and migrated to lymph
nodes after antigen uptake in IL-37tg mice. When hapten-sensitized DCs were
adoptively transferred to WT mice, antigen challenge was greatly impaired in mice
receiving DCs from IL-37tg mice compared with those receiving DCs from WT mice
(-60%; P < 0.01 at 48 h). In DCs isolated from IL-37tg mice, LPS-induced increase
of MHC II and costimulatory molecule CD40 was reduced by 51 and 31%,
respectively. In these DCs, release of IL-1?, IL-6, and IL-12 was reduced whereas
IL-10 secretion increased (37%). Consistent with these findings, DCs from IL-37tg
mice exhibited a lower ability to stimulate syngeneic and allogeneic naive T
cells as well as antigen-specific T cells and displayed enhanced induction of T
regulatory (Treg) cells (86%; P < 0.001) in vitro. Histological analysis of CHS
skin in mice receiving hapten-sensitized DCs from IL-37tg mice revealed a marked
reduction in CD8(+) T cells (-74%) but an increase in Treg cells (2.6-fold).
Together, these findings reveal that DCs expressing IL-37 are tolerogenic,
thereby impairing activation of effector T-cell responses and inducing Treg
cells. IL-37 thus emerges as an inhibitor of adaptive immunity.
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