optimized-mouse-model-to-induce-colitis-associated-colon-cancer-using

Optimized Mouse Model to Induce Colitis-Associated Colon Cancer using Azoxymethane and Dextran Sulfate Sodium for Tumor Immunology and Therapy Studies

Azoxymethane (AOM, a DNA-damaging agent) and dextran sulfate sodium (DSS, a colitis-promoting agent) can induce tumors in the large intestine of mice with ...

H. Lee Moffitt Cancer Center and Research Institute

The networks of transcription factors (TFs) that control intestinal-resident memory CD8 T (T) cells, including multipotency and effector programs, are poorly understood. In this work, we investigated the role of the TF Bcl11b in T cells during infection with  using mice with post-activation, conditional deletion of Bcl11b in CD8 T cells. Conditional deletion of Bcl11b resulted in increased numbers of intestinal T cells and their precursors as well as decreased splenic effector and circulating memory cells and precursors. Loss of circulating memory cells was in part due to increased intestinal homing of  circulating precursors, with no major alterations in their programs.  T cells had altered transcriptional programs, with diminished expression of multipotent/multifunctional (MP/MF) program genes, including , and up-regulation of the effector program genes, including  Bcl11b also limits the expression of Ahr, another TF with a role in intestinal CD8 T cell differentiation. Deregulation of T programs translated into a poor recall response despite T cell accumulation in the intestine. Reduced expression of MP/MF program genes in Bcl11b T cells was linked to decreased chromatin accessibility and a reduction in activating histone marks at these loci. In contrast, the effector program genes displayed increased activating epigenetic status. These findings demonstrate that Bcl11b is a frontrunner in the tissue residency program of intestinal memory cells upstream of Tcf1 and Blimp1, promoting multipotency and restricting the effector program.

Shamima Islam

Biography

JoVE Journal Publications

Other Publications