IL12RB1 allelic expression imbalance in polarized human TH cells

Abstract Allelic Expression Imbalance (AEI) occurs when two alleles of a given gene are expressed at different levels, either due to epigenetic inactivation and/or genetic variation in regulatory regions. Human autosomal genes are widely presumed to be equally expressed from both alleles (biallelic expression); this is not always the case, however, as AEI affects expression of odorant receptor and adhesin genes in neurons, as well as immunoglobulin (Ig) and T-cell receptor (TCR) genes in lymphocytes. Ig and TCR gene AEI is an important regulator of immune development and disease resistance; therefore, it is reasonable to believe AEI of other immune receptors may similarly impact immune development and disease resistance. Here we demonstrate that the human cytokine receptor gene Interleukin 12 Receptor Beta 1 (IL12RB1) exhibits AEI in differentiated T cells, as measured by a significant deviation of the allelic mRNA expression ratios from that of the allelic gDNA ratios. Specifically, naïve human CD4+ T cells were purified from healthy adult donors and incubated with polarizing cytokines to drive their differentiation into specific T helper subsets (e.g. TH0 cocktail: IL-2. TH1 cocktail: IL-2, anti-IL-4, IL-12. TH17 cocktail: IL-2, IL-1b, TGF-b1, IL-23, anti-IFNg, anti-IL-4). The extent of IL12RB1 AEI was then quantified and related to T cell expression of IFNg (TH1) and IL17 (TH17). Collectively, our data suggest that IL12RB1 AEI associates with the expression of anti-mycobacterial effector genes in T cells. Future experiments will determine the epigenetic or molecular mechanism behind IL12RB1 AEI.