IL-27: An endogenous constitutive repressor of human monocytes

Area of Science:

• Immunology
• Cytokine Biology
• Innate and Adaptive Immunity

Background:

• Interleukin-27 (IL-27) exhibits dual roles, acting as both pro-inflammatory and anti-inflammatory cytokine.
• IL-27 influences T helper cell differentiation, including T helper 1 (Th1), T helper 17 (Th17), and T regulatory 1 (Tr1) cells.
• Human antigen-presenting cells, particularly monocytes, are significant producers and responders to IL-27.

Purpose of the Study:

• To investigate the endogenous role of IL-27 in regulating human monocytes.
• To determine the impact of monocyte-derived IL-27 on CD4+ T cell responses, specifically Th17 cells.
• To explore the potential involvement of IL-27 in type 1 diabetes (T1D) pathogenesis.

Main Methods:

• Utilized anti-IL-27 neutralizing antibodies to block endogenous IL-27 activity in human monocyte cultures ex vivo.
• Assessed the production of pro-inflammatory cytokines following IL-27 neutralization.
• Analyzed the effects on CD4+ T cell cytokine production (e.g., IL-17A) and CD39 expression on monocytes.

Main Results:

• Neutralizing endogenous IL-27 enhanced the production of pro-inflammatory cytokines by human monocytes.
• Blocking IL-27 led to increased IL-17A production by CD4+ T cells.
• Down-regulation of CD39, an IL-17 modulating ectonucleotidase, was observed on monocytes upon IL-27 neutralization.
• Monocytes from type 1 diabetes (T1D) subjects showed increased IL-27 production ex vivo.

Conclusions:

• IL-27 acts as an endogenous suppressor of human monocytes, modulating their pro-inflammatory cytokine output.
• IL-27 influences CD4+ T cell phenotype, particularly suppressing Th17 cell responses.
• Elevated IL-27 production in T1D monocytes may represent a negative feedback mechanism to control inflammation.