Distinct mechanisms regulate IL1B gene transcription in lymphoid CD4 T cells and monocytes

Abstract

Interleukin 1β is a pro-inflammatory cytokine important for both normal immune responses and chronic inflammatory diseases. The regulation of the 31 kDa proIL-1β precursor coded by the IL1B gene has been extensively studied in myeloid cells, but not in lymphoid-derived CD4 T cells. Surprisingly, we found that some CD4 T cell subsets express higher levels of proIL-1β than unstimulated monocytes, despite relatively low IL1B mRNA levels. We observed a significant increase in IL1B transcription and translation in CD4 T cells upon ex vivo CD3/CD28 activation, and a similar elevation in the CCR5+ effector memory population compared to CCR5- T cells in vivo. The rapid and vigorous increase in IL1B gene transcription for stimulated monocytes has previously been associated with the presence of Spi-1/PU.1 (Spi1), a myeloid-lineage transcription factor, pre-bound to the promoter. In the case of CD4 T cells, this increase occurred despite the lack of detectable Spi1 at the IL1B promoter. Additionally, we found altered epigenetic regulation of the IL1B locus in CD3/CD28-activated CD4 T cells. Unlike monocytes, activated CD4 T cells possess bivalent H3K4me3+/H3K27me3+ nucleosome marks at the IL1B promoter, reflecting low transcriptional activity. These results support a model in which the IL1B gene in CD4 T cells is transcribed from a low-activity bivalent promoter independent of Spi1. Accumulated cytoplasmic proIL-1β may ultimately be cleaved to mature 17 kDa bioactive IL-1β, regulating T cell polarization and pathogenic chronic inflammation.

Screening of immune-related differentially expressed genes from primary lymphatic organs of broilers fed with probiotic bacillus cereus PAS38 based on suppression subtractive hybridization

“…In this experiment, 6 cytokines were selected to detect the expression changes after the interference of differential genes. Among them, IL-1B , IL-2 and IL-6 are all common interleukins, they play an important role in lymphocytes activation, production of cytokines, antibodies and complement [ 40 – 42 ]. And MYD88 , IRF1 and TLR4 , play key roles in pathogen recognition, activation and conduction of immune signals [ 43 – 45 ].…”

Transcriptional Regulation of Inflammasomes

“…IL1B expression in CD4 + T cells (and particularly the CCR5 + subset) is up-regulated following TCR engagement with different co-stimulation signals. CD4 + T cells do not present detectable amounts of PU.1 protein [138] even after TCR engagement. Accordingly, IL1B promoter in resting T cells is not accessible and does not present the poised architecture observed in monocytes [119].…”

“…This mechanism is associated with an increase in the activating epigenetic histone modifications (H3K4me3 and H3K9ac), a corresponding decrease in the inhibiting modification (H3K27me3) at the Il1b promoter site and Pol II enrichment throughout Il1b gene upon T cell activation. In contrast to housekeeping genes transcribed at high level, inhibitory H3K27me3 marks persist on the Il1b promoter resulting in a bivalent H3K4me3 + /H3K27me3 + low-activity promoter [138].…”

Methamphetamine Enhances HIV-1 Replication in CD4+ T-Cells via a Novel IL-1β Auto-Regulatory Loop

“…Unlike extracellular IL-1β, which increased after 1 day of Meth treatment, IL-1β mRNA showed increased expression only on day 3 (Figure 2A). Notably, IL-1β release and mRNA expression are controlled by distinct mechanisms (45). In addition, CD4 + T-cells constitutively express pro-IL-1β in their cytoplasm (46).…”