IL‐12 and IL‐23: master regulators of innate and adaptive immunity

Abstract

Initiation of an effective immune response requires close interactions between innate and adaptive immunity. Recent advances in the field of cytokine biology have led to an increased understanding of how myeloid cell-derived factors regulate the immune system to protect the host from infections and prevent tumor development. In this review, we focus on the function of interleukin (IL)-23, a new member of the IL-12 family of regulatory cytokines produced by activated macrophages and dendritic cells. We propose that IL-12 and IL-23 promote two distinct immunological pathways that have separate but complementary functions. IL-12 is required for antimicrobial responses to intracellular pathogens, whereas IL-23 is likely to be important for the recruitment and activation of a range of inflammatory cells that is required for the induction of chronic inflammation and granuloma formation. These two cytokines work in concert to regulate cellular immune responses critical for host defense and tumor suppression.

IL12B polymorphisms are linked but not associated with Plasmodium falciparum parasitemia: a familial study in Burkina Faso

“…IL-12, which was first described as natural killer cell stimulatory factor, 10 is a primary inducer of the development of T-helper 1 (Th1) lymphocytes characterized by the production of IFNg, and IL-23 drives the development of Th17 lymphocytes characterized by the production of IL-17. 11 There is a growing body of evidence for a key role of IL-12 in the immune response directed against Plasmodium species, whereas IL-23 was only recently proposed to be involved in malaria. 12 Neutralization of endogenous IL-12 with anti-IL-12p40 and anti-IL-12p35 antibodies in P. chabaudiinfected mice resulted in an increase of parasitemia, 13 whereas administration of recombinant IL-12 in mice and monkeys conferred a protection from Plasmodium species infection.…”

CD4 T cells producing pro-inflammatory interleukin-17 mediate high pathology in schistosomiasis

“…However, other pro-inflammatory mediators produced by the Th IL-17 cells, including TNF-α, IL-6, IL-8 and other chemokines (Kolls & Linden 2004, Langrish et al 2004, may also play a significant role in the pathology. One apparent mechanism used by Th IL-17 cells to cause pathology is through recruitment of granulocytes, which in the case of the schistosome egg-granulomas, may include the eosinophils.…”

Adenovirus-mediated gene transfer of interleukin-23 shows prophylactic but not therapeutic antitumor effects

“…7,30 Stat4 is essential for IL-12-mediated responses including perforin-mediated NK cell activity, 31,32 whereas Stat3 may be involved in mediating more general types of signals such as those for cell growth and survival. 33,34 It was recently reported that the expression of IL-23 was increased in a human tumor, and that the growth of the transplanted tumor was restricted in mice depleted for IL-23p19 or IL-23R.…”