Interleukin 27: a double-edged sword for offense and defense

Abstract

Cytokine-mediated immunity plays a crucial role in the pathogenesis of various diseases including infection and autoimmune diseases. IL-27, along with IL-12, -23, and -35, belongs to the IL-12 cytokine family. These family members play roles in regulation of Th cell differentiation. IL-27 is unique in that although it induces Th1 differentiation, the same cytokine suppresses immune responses. In the absence of IL-27-mediated immunosuppression, hyperproduction of various proinflammatory cytokines concomitant with severe inflammation is observed. The immunosuppressive effects of IL-27 depend on IL-2 suppression, inhibition of Th17 development, and induction of IL-10 production. Administration of IL-27 suppresses some diseases of autoimmune or allergic origin, demonstrating its potential in therapy of diseases mediated by inflammatory cytokines. In this review, we discuss recent studies about the role of IL-27 in immune regulation in view of its pro- and anti-inflammatory properties and possible therapeutic application.

IL-27, a Cytokine, and IFN-λ1, a Type III IFN, Are Coordinated To Regulate Virus Replication through Type I IFN

“…The signaltransduction receptor complex for IL-27 is composed of the cytokine receptor IL-27Ra (WSX-1 or alternatively T cell cytokine receptor [TCCR]) and the gp130 protein (2). IL-27 is produced mainly by activated macrophages and dendritic cells (DCs) and is a cytokine that regulates Th function during autoimmune and pathogen-induced immune responses (3,4). In early studies, IL-27 was initially described as a proinflammatory cytokine that promoted Th1 responses (1,5).…”

Interleukin‐27: A master regulator in inflammation

“…IL-27, an IL-12 family member, is a heterodimeric cytokine consisting of an IL-12 p40-related protein (Epstein-Barr virus-induced gene 3) and an IL-12 p35-like protein (p38) (1). IL-27 signals through a receptor complex consisting of IL-27␣ (also known as WSX-1 or T cell cytokine receptor) and the protein gp130 (which is also used by the IL-6 type family of cytokines).…”

“…IL-27 is expressed mainly on activated macrophages and dendritic cells; in contrast, IL-27 receptor (IL-27R) is widely expressed and is detected on naive T cells, natural killer (NK) cells, monocytes, mast cells, vascular endothelium, keratinocytes, activated B cells, Langerhans' cells, and dendritic cells (1). IL-27 is expressed at sites of inflammation in autoimmune/inflammatory diseases, such as RA, PsA, systemic sclerosis (SSc), inflammatory bowel disease (IBD), multiple sclerosis, and sarcoidosis (1,(4)(5)(6). IL-27 is predominantly produced shortly after stimulation of antigen-presenting cells by Toll-like receptor (TLR) ligands or infectious agents (1,2).…”

“…IL-27 is expressed at sites of inflammation in autoimmune/inflammatory diseases, such as RA, PsA, systemic sclerosis (SSc), inflammatory bowel disease (IBD), multiple sclerosis, and sarcoidosis (1,(4)(5)(6). IL-27 is predominantly produced shortly after stimulation of antigen-presenting cells by Toll-like receptor (TLR) ligands or infectious agents (1,2). IL-27 subunits can also be induced in response to host-derived inflammatory stimuli such as CD40 and IL-1␤, through myeloid differentiation factor 88-mediated pathways (7,8).…”

“…Initial studies examining IL-27 function demonstrated a role in promoting early stages of activation of naive CD4ϩ T and Th1 cell differentiation (1,3,4). IL-27 can synergize with IL-12 to promote production of interferon-␥ (IFN␥) by CD4ϩ, CD8ϩ, and NK T cells (2).…”