Making many from few: IL-12p40 as a model for the combinatorial assembly of heterodimeric cytokines

Abstract

How dendritic cells (DCs) gather information from the local milieu at a site of infection or injury and communicate this to influence adaptive immunity is not well understood. We and others have reported that soon after microbial encounter, DCs secrete the p40 subunit of IL-12, by itself, in a monomeric form. Based on recent data that this p40 monomer subsequently associates with p35 released from other cells to generate functional IL-12, we proposed that p40 can function as a DC-derived probe which samples the composition of the local milieu by looking for other binding partners. In this opinion, we discuss how such a sampling function might generate an elaborate combinatorial “code” of heterodimeric cytokines, capable of conveying location-specific information to cells downstream of DC activation, including NK and T cells.

Polyphenol Effects on Splenic Cytokine Response in Post-Weaning Contactin 1-Overexpressing Transgenic Mice

“…IL-12 is a Th1-induced cytokine, released by splenic dendritic cells upon antigenic activation [34]. As shown in Figure 1, at post-natal day 8, IL-12 could not be detected in supernatants from wt splenocytes in the absence of treatment or in mice undergoing PMA stimulation and in suckling pups which received milk from dams administered with polyphenols (POP mice).…”

A pilot, open‐label, 8‐week study evaluating the efficacy, safety and tolerability of adjunctive minocycline for the treatment of bipolar I/II depression

“…The IL‐12/23p40 homodimer has been reported to act as an antagonist of IL‐12p70 by binding to the IL‐12 receptor complex in mice. Conversely, other studies indicate that the IL‐12/23p40 homodimer acts as an agonist and is associated with chemoattraction of macrophages and dendritic cells (reviewed in ). Consistent with a potential antagonistic effect, levels of IL‐12p70 were found to be reduced from baseline to week 8.…”

Oral recombinant human or mouse lactoferrin reducesMycobacterium tuberculosisTDM induced granulomatous lung pathology

“…IL-12p40 can form various heterodimers, leading to formations of IL-12p70 and IL-23, to name 2 cytokines important for differentiation of naive T cells, T cell helper type 1, and T cell helper type 17, respectively (Abdi and Singh 2015). While T cell helper type 1 is needed for protection against MTB infection and TB, the role of T cell helper type 17 is still being debated (O’Garra et al 2013).…”