CD4 T-cell cytokines synergize to induce proliferation of malignant and nonmalignant innate intraepithelial lymphocytes

• DOI: 10.1073/pnas.1620036114
• Publication Date: 2017-01-04T01:50:20Z
• Authors: Yvonne M. C. Kooy...; Dagmar Bouwer; George M. C. Janssen; Allan Thompson; Martijn H. Brugman; Frederike Schmitz; Arnoud H. de Ru; Tom van Gils; Gerd Bouma; Jon J. van Rood; Peter A. van Veelen; M. Luisa Mearin; Chris J. Mulder; Frits Koning; Jeroen van Bergen
• Keywords: CD4-Positive T-Lymphocytes; Interleukin-15; 0301 basic medicine; Duodenum; Tumor Necrosis Factor-alpha; Interleukins; Apoptosis; Drug Synergism; refractory celiac disease; enteropathy-associated T-cell lymphoma; Recombinant Proteins; 3. Good health; Celiac Disease; 03 medical and health sciences; Cytokines; Humans; Interleukin-2; intraepithelial lymphocyte; Transcriptome; Intraepithelial Lymphocytes; celiac disease; small-molecule inhibitor; Cells, Cultured; Cell Proliferation

SignificanceRefractory celiac disease type II (RCDII) is a severe variant of celiac disease, an autoimmune disorder of the small intestine caused by inflammatory T-cell responses to gluten, a common food protein. Typical of RCDII is the presence of aberrant lymphocytes in the duodenal epithelium, which often give rise to a lethal lymphoma. A single growth factor promoting the expansion of aberrant cells has been identified: epithelial cell-derived IL-15. The experiments described in this paper identify three additional growth factors—TNF, IL-2, and IL-21—produced by gluten-specific T cells. Thus, these findings suggest a potential mechanism for the contribution of gluten-specific T cells to RCDII.