Inflammatory Bowel Diseases (IBD), including Crohn’s disease and ulcerative colitis, remain among the most complex and persistent autoimmune disorders, with limited therapeutic options that precisely modulate the immune response. In this context, a recent study has uncovered a key immunoregulatory mechanism involving Poly(ADP-ribose) Polymerase-1 (PARP1) and High Mobility Group Box 1, which opens promising avenues for future interventions.
A particularly innovative aspect of the study involved investigating the role of extracellular HMGB1 in dendritic cell-mediated T cell polarization. To this scope, researchers employed the HMGB1 B box domain (0.1–1 μg/ml), supplied by HMGBiotech, as a functional reagent to modulate DC activity in vitro.
The HMGB1 B box, known to mimic the pro-inflammatory action of full-length HMGB1, was used alongside dipotassium glycyrrhizate, an extracellular HMGB1 inhibitor, to determine the alarmin’s contribution to DC polarization. The results demonstrated that:
- PARP-1KO dendritic cells (DCs), when exposed to HMGB1 B box, maintained a stronger Treg-inducing profile than WT DCs, indicating a partial independence from extracellular HMGB1 signals.
- Wild type (WT) DCs, however, were more sensitive to HMGB1 signaling, promoting Th17 cell differentiation under the same conditions.
The outcomes reinforce the context-dependent immunomodulatory role of HMGB1, particularly during sterile inflammation in the gut. Importantly, they also validate the HMGB1 B box as a reliable tool for dissecting alarmin-mediated immune mechanisms.
These findings position PARP1 as a key molecular switch in orchestrating gut immune homeostasis, partly by modulating DC functionality and their response to alarmins like HMGB1. In diseases like IBD, where restoring Treg/Th17 balance is a therapeutic priority, both PARP1 targeting and HMGB1 modulation emerge as attractive strategies.
At HMGBiotech, we are proud to contribute to this growing body of knowledge by providing high-quality recombinant HMGB1 proteins, including the biologically active HMGB1 B box domain used in this study.
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Read the full article about the study: https://www.sciencedirect.com/science/article/pii/S0165247824000865
