Heat shock factor 1 drives regulatory T-cell induction to limit murine intestinal inflammation.

The heat shock response is a critical component of the inflammatory cascade that prevents misfolding of new proteins and regulates immune responses. Activation of clusters of differentiation (CD)4 T cells causes an upregulation of heat shock transcription factor, heat shock factor 1 (HSF1). We hypothesized that HSF1 promotes a pro-regulatory phenotype during inflammation.

The Tox Gene Encodes Two Proteins with Distinct and Shared Roles in Gene Regulation.

Here we report that the murine Tox gene encodes two proteins from a single mRNA, and we investigate the mechanism of production and function of these proteoforms. The annotated thymocyte selection-associated HMG-box protein (TOX) coding sequence is predicted to produce a 526-aa protein (TOXFL). However, Western blots reveal two bands.

Alternative activation generates IL-10 producing type 2 innate lymphoid cells.

Type 2 innate lymphoid cells (ILC2) share cytokine and transcription factor expression with CD4 T2 cells, but functional diversity of the ILC2 lineage has yet to be fully explored. Here, we show induction of a molecularly distinct subset of activated lung ILC2, termed ILC2. These cells produce IL-10 and downregulate some pro-inflammatory genes.

p53 Regulates Progenitor Cell Quiescence and Differentiation in the Airway.

Mechanisms that regulate progenitor cell quiescence and differentiation in slowly replacing tissues are not fully understood. Here, we demonstrate that the tumor suppressor p53 regulates both proliferation and differentiation of progenitors in the airway epithelium. p53 loss decreased ciliated cell differentiation and increased the self-renewal and proliferative capacity of club progenitors, increasing epithelial cell density.

Targeted inhibition of heat shock protein 90 suppresses tumor necrosis factor-α and ameliorates murine intestinal inflammation.

Inflammatory bowel diseases are chronic intestinal inflammatory diseases thought to reflect a dysregulated immune response. Although antibody-based inhibition of tumor necrosis factor-α (TNF-α) has provided relief to many inflammatory bowel diseases patients, these therapies are either ineffective in a patient subset or lose their efficacy over time, leaving an unmet need for alternatives. Given the critical role of the heat shock response in regulating inflammation, this study proposed to define the impact of selective inhibition of heat shock protein 90 (HSP90) on intestinal inflammation.

Rapid infliximab infusions in pediatric inflammatory bowel disease.

The manufacturer of infliximab recommends infusion over 2 to 3 hours. In 16 children who received 133 standard 2- to 3-hour infusions, followed by fifty 1-hour infusions, chart review revealed a frequency of infusion reactions of 2% with both infusion protocols (3/133 and 1/50). The first reaction with the rapid infusion occurred in a patient who had experienced an identical reaction with the longer infusion, but was mistakenly not premedicated.