Interleukin-15-Dependent T-Cell-like Innate Intraepithelial Lymphocytes Develop in the Intestine and Transform into Lymphomas in Celiac Disease.

The nature of gut intraepithelial lymphocytes (IELs) lacking antigen receptors remains controversial. Herein we showed that, in humans and in mice, innate intestinal IELs expressing intracellular CD3 (iCD3(+)) differentiate along an Id2 transcription factor (TF)-independent pathway in response to TF NOTCH1, interleukin-15 (IL-15), and Granzyme B signals. In NOTCH1-activated human hematopoietic precursors, IL-15 induced Granzyme B, which cleaved NOTCH1 into a peptide lacking transcriptional activity.

Impairment of TNF-alpha production and action by imidazo[1,2- alpha] quinoxalines, a derivative family which displays potential anti-inflammatory properties.

In a previous study, we analysed the synthesis and properties of a series of imidazo[1,2-alpha]quinoxalines designed in our laboratory as possible imiquimod analogues. We found that these imidazo[1,2-alpha]quinoxalines were in fact potent inhibitors of phosphodiesterase 4 enzymes (PDE4). PDE4 inhibition normally results in an increase in intracellular cAMP which, in PBMC, induces the suppression of TNF-alpha mRNA transcription and thus cytokine synthesis.