IL‐23 up‐regulates IL‐10 and induces IL‐17 synthesis by polyclonally activated naive T cells in human

Abstract

Interleukin (IL)-23 is a heterodimeric cytokine of the IL-12 family. Human IL-23 is known to induce interferon (IFN)-c production and proliferation in T cells, preferentially in the CD45RO + memory subset. Yet, its role in the differentiation of human naive T cells remains largely unknown. We investigated the effect of recombinant human (rh)IL-23 on cord blood CD4 + and CD8 + T cells during polyclonal activation. The IL-23 receptor complex was not detectable in resting naive T cells. Nevertheless, both IL-23 receptor subunits, IL-12Rb1 and IL-23R, were rapidly induced after activation in both naive CD4 + and CD8 + T cells. In both cell types, rhIL-23 enhanced IFN-c production. This effect was demonstrable as early as 2 days after activation, illustrating that a functional IL-23 receptor is rapidly induced in naive T cells upon activation. In naive CD8 + T cells, rhIL-23 specifically induced the secretion of IL-17, a pro-inflammatory cytokine. Moreover, rhIL-23 significantly increased the production of IL-10 in both naive CD4 + and CD8 + T cells. IL-17 and IL-10 levels were not affected by the addition of rhIL-12. We conclude that IL-23 induces a specific cytokine profile, remarkably distinct from IL-12, in activated human naive T cells.

TLR2‐activated human langerhans cells promote Th17 polarization via IL‐1β, TGF‐β and IL‐23

“…By detection of IL-1b, IL-6, IL-23, and TGF-b we found cytokines that recently have been proposed to be crucial for Th17 commitment [15][16][17][18][19]. However, even in human T cells, IL-23 seems to be responsible rather for enhancement than commitment of IL-17 [34], but in human CD8 1 T cells also IL-17 induction was observed [35]. The cytokine profile found in our experiments may be specific for the CD1c 1 phenotype, which is consistent with detection of IL-6 and IL-1b in CD1c 1 circulating DC, stimulated by TLR agonists [18].…”

Increased circulating interleukin (IL)-23 in children with malarial anemia: In vivo and in vitro relationship with co-regulatory cytokines IL-12 and IL-10

“…Although IL-10 can suppress both IL-23 and IL-12 [22,23], IL-23 can also promote IL-10 production by activated lymphocytes [46]. Results presented here showing that the relative expression of IL-10 to IL-23 progressively increased with increasing anemia severity may suggest that IL-10 could have a suppressive effect on IL-23 production.…”

Inhibitory Effect of Recombinant IL-25 on the Development of Dextran Sulfate Sodium-Induced Experimental Colitis in Mice

“…On the other hand, IL-23 (31,32) and TGF-1 (28, 33) have been strongly reported to be involved in the development of IL-17-producing CD4 + T cells via a new T cell subset Th17. In addressing the impact of IL-23 and TGF-1 in the differentiation of naïve T cells into Th17 cells, we further investigated the development of IL-17-producing CD4 + /CD8 + T cells in splenic lymphocytes.…”