Lipopolysaccharide shock reveals the immune function of indoleamine 2,3-dioxygenase 2 through the regulation of IL-6/stat3 signalling

Abstract

Indoleamine 2,3-dioxygenase 2 (Ido2) is a recently identified catalytic enzyme in the tryptophan-kynurenine pathway that is expressed primarily in monocytes and dendritic cells. To elucidate the biological role of Ido2 in immune function, we introduced lipopolysaccharide (LPS) endotoxin shock to Ido2 knockout (Ido2 KO) mice, which led to higher mortality than that in the wild type (WT) mice. LPS-treated Ido2 KO mice had increased production of inflammatory cytokines (including interleukin-6; IL-6) in serum and signal transducer and activator of transcription 3 (stat3) phosphorylation in the spleen. Moreover, the peritoneal macrophages of LPS-treated Ido2 KO mice produced more cytokines than did the WT mice. By contrast, the overexpression of Ido2 in the murine macrophage cell line (RAW) suppressed cytokine production and decreased stat3 expression. Finally, RAW cells overexpressing Ido2 did not alter nuclear factor κB (NF-κB) or stat1 expression, but IL-6 and stat3 expression decreased relative to the control cell line. These results reveal that Ido2 modulates IL-6/stat3 signalling and is induced by LPS, providing novel options for the treatment of immune disorders.

Genome-wide association study of non-alcoholic fatty liver and steatohepatitis in a histologically characterised cohort☆

“…41,42 The signal on chromosome 8 relates to an area between IDO2 and TC1. Of potential relevance to NAFLD, both genes have roles in modulating inflammation with IDO2 inducible by lipopolysaccharide and contributing to immune function 43 while TC1 modulates NF-jB signalling. Further investigation of these variants is needed.…”

Indoleamine 2,3-Dioxygenase 2 Immunohistochemical Expression in Resected Human Non-small Cell Lung Cancer: A Potential New Prognostic Tool

“…Moreover, in a previous study (19) we reported a nuclear labeling for IDO1 in NSCLC. However, it is generally not known how these two molecules would act at nuclear level, but the observation that some tumors present a nuclear localization of both IDO1 and IDO2 may suggest a signaltransducing function (13,30), something already noted about IDO1 (31).…”

Indoleamine 2,3-Dioxygenase 2 Deficiency Exacerbates Imiquimod-Induced Psoriasis-Like Skin Inflammation

“…The mechanism by which IDO2 controls IMQ-induced dermatitis remains unclear. In our previous report, IDO2 was demonstrated to be important in the regulation of STAT3 signaling using a lipopolysaccharide-induced endotoxin shock model [ 40 ]. STAT3 participates in signaling downstream of multiple cytokines implicated in psoriasis, such as IL-6, IL-10, IL-20, IL-22, and IL-23, and may have a role in mediating the innate immune response in psoriatic epidermis [ 41 ].…”