Regulation of IL-10 and IL-12 production and function in macrophages and dendritic cells

Abstract

Interleukin-10 and Interleukin-12 are produced primarily by pathogen-activated antigen-presenting cells, particularly macrophages and dendritic cells. IL-10 and IL-12 play very important immunoregulatory roles in host defense and immune homeostasis. Being anti- and pro-inflammatory in nature, respectively, their functions are antagonistically opposing. A comprehensive and in-depth understanding of their immunological properties and signaling mechanisms will help develop better clinical intervention strategies in therapy for a wide range of human disorders. Here, we provide an update on some emerging concepts, controversies, unanswered questions, and opinions regarding the immune signaling of IL-10 and IL-12.

Keywords: IL-10; IL-12; immune signaling.

Figure 1.. Transcriptional regulation of IL-12p40 (IL12b) in antigen-presenting cells.

The data are drawn primarily from macrophage studies. In dendritic cells, c-Rel is not required for IL12B transcription. F1 denotes a large molecular complex containing multiple transcription factors binding to the human IL12b promoter . Green-arrowed lines indicate a stimulatory role for IL12b transcription, whereas red-arrowed lines denote the reverse. Continuous short arrows denote multiple steps involved that are not specified in details. Dashed lines indicate undetermined signaling pathway. The promoter coordinates are with respect to the transcription start site, designated +1, of the human IL12b gene. GAP-12 is a putative transcriptional repressor of unidentified nature that is induced by IL-4 or PGE2 treatment of human monocytes . The asterisks denotes controversial transcriptional factors that are defined as repressors by mouse knockout studies but as activators in some in vitro studies (see text for details). Akt, Ak strain transforming; AP-1; activating protein 1; cAMP, cyclic adenosine monophosphate; C/EBP, CCAAT enhancer-binding protein; CpG, cytosine-phosphate-guanine; ds, double-stranded; Ets2, E26 2; GAP-12, GATA sequence in the IL-12 promoter; IRF, interferon regulatory factor; JNK, c-Jun N-terminal kinase; MyD88, myeloid differentiation primary response gene 88; mTOR, mammalian target of rapamycin; PGE2, prostaglandin E2; PK, protein kinase; Pol, polymerase; PU.1, purine.1; RLR, retinoic acid-inducible gene-I-like receptor; STAT, signal transduction and transcription; TLR, Toll-like receptor.