title: Suppression of antigen-specific adaptive immunity by IL-37 via induction of tolerogenic dendritic cells.
abstract: 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-1β, 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.
authors.affiliation: Departments of Dermatology and.
authors.forename: Yuchun
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Departments of Dermatology and Department of Plastic and Reconstruct Surgery, First Affiliated Hospital of Shantou University Medical College, Shantou City 515041, People's Republic of China;
authors.forename: Xiangna
authors.initials: X
authors.lastname: Cai
authors.affiliation: Departments of Dermatology and.
authors.forename: Sucai
authors.initials: S
authors.lastname: Liu
authors.affiliation: Departments of Dermatology and Department of Plastic and Reconstruct Surgery, First Affiliated Hospital of Shantou University Medical College, Shantou City 515041, People's Republic of China;
authors.forename: Sen
authors.initials: S
authors.lastname: Wang
authors.affiliation: The Ritchie Centre, Monash Institute of Medical Research, Monash University, Melbourne, VIC 3800, Australia;
authors.forename: Claudia A
authors.initials: CA
authors.lastname: Nold-Petry
authors.affiliation: The Ritchie Centre, Monash Institute of Medical Research, Monash University, Melbourne, VIC 3800, Australia;
authors.forename: Marcel F
authors.initials: MF
authors.lastname: Nold
authors.affiliation: Children's Hospital, Ludwig-Maximilians University, 80539 Munich, Germany; and.
authors.forename: Philip
authors.initials: P
authors.lastname: Bufler
authors.affiliation: Departments of Dermatology and Denver Veterans Affairs Medical Center, Denver, CO 80220.
authors.forename: David
authors.initials: D
authors.lastname: Norris
authors.affiliation: Medicine, University of Colorado Denver, Aurora, CO 80045; mayumi.fujita@ucdenver.edu cdinarello@mac.com.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Dinarello
authors.affiliation: Departments of Dermatology and Denver Veterans Affairs Medical Center, Denver, CO 80220 mayumi.fujita@ucdenver.edu cdinarello@mac.com.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Fujita
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D002465:Cell Movement; D002633:Chemotaxis; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology*; D003877:Dermatitis, Contact / Q000276:immunology; D004139:Dinitrofluorobenzene / Q000737:chemistry; D005434:Flow Cytometry; D006241:Haptens / Q000737:chemistry; D006801:Humans; D007113:Immunity, Innate; D007375:Interleukin-1 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010587:Phagocytosis; D012867:Skin / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology
chemical_list: D016207:Cytokines; D006241:Haptens; C508587:IL37 protein, human; D007375:Interleukin-1; D004139:Dinitrofluorobenzene
keywords: allergic contact dermatitis; skin inflammation; tolerance