Abstract

The new Cancer Inflammation Program has inspired two new projects in colon cancer that diverge from our previous focus on IL-7. One project involves IL-17A , IL-17 F and IL-25. These are T cell cytokines that are produced by cells that strongly promote the intestinal inflammation that leads to colon cancer. It has not been determined where IL-17 and 25 are produced during this inflammatory response. We have developed knockin reporter mice for the two IL-17 genes using two colors and for IL-25. This will enable us to visualize cells producing these critical inflammatory cytokines during bowel inflammation leading to colon cancer. A second project aims to inhibit the bowel inflammation leading to colon cancer. IL-27 and IL-35 are suppressive cytokines that we have cloned into the food bacterium, Lactococcus lactis. These engineered bacteria were given orally to mice with experimentally-induced fatal IBD. IL-27 rescued all mice from IBD and death and therefore is an extremely promising therapeutic. The mechanism appears to be through secondary induction of the suppressive cytokine IL-10, and subsequent inhibition of many inflammatory cytokines such as IL-23 and IL-6.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC011150-02
Application #
8157656
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2010
Total Cost
$511,917
Indirect Cost

  Institution

Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Porter, Ross John; Andrews, Caroline; Brice, Daniel Paul et al. (2018) Can We Target Endogenous Anti-inflammatory Responses as a Therapeutic Strategy for Inflammatory Bowel Disease? Inflamm Bowel Dis :
Aiello, Francesca B; Guszczynski, Tad; Li, Wenqing et al. (2018) IL-7-induced phosphorylation of the adaptor Crk-like and other targets. Cell Signal 47:131-141
Senkevitch, Emilee; Li, Wenqing; Hixon, Julie A et al. (2018) Inhibiting Janus Kinase 1 and BCL-2 to treat T cell acute lymphoblastic leukemia with IL7-R? mutations. Oncotarget 9:22605-22617
Francois, Bruno; Jeannet, Robin; Daix, Thomas et al. (2018) Interleukin-7 restores lymphocytes in septic shock: the IRIS-7 randomized clinical trial. JCI Insight 3:
Andrews, Caroline; McLean, Mairi H; Durum, Scott K (2018) Cytokine Tuning of Intestinal Epithelial Function. Front Immunol 9:1270
Cramer, Sarah D; Hixon, Julie A; Andrews, Caroline et al. (2018) Mutant IL-7R? and mutant NRas are sufficient to induce murine T cell acute lymphoblastic leukemia. Leukemia 32:1795-1882
Yoshimura, Teizo; McLean, Mairi H; Dzutsev, Amiran K et al. (2018) The Antimicrobial Peptide CRAMP Is Essential for Colon Homeostasis by Maintaining Microbiota Balance. J Immunol 200:2174-2185
Rodriguez-Palacios, Alexander; Harding, Andrew; Menghini, Paola et al. (2018) The Artificial Sweetener Splenda Promotes Gut Proteobacteria, Dysbiosis, and Myeloperoxidase Reactivity in Crohn's Disease-Like Ileitis. Inflamm Bowel Dis 24:1005-1020
Shen, Wei; Li, Wenqing; Hixon, Julie A et al. (2017) Visualization of IL-22-expressing Lymphocytes Using Reporter Mice. J Vis Exp :
McLean, Mairi H; Andrews, Caroline; Hanson, Miranda L et al. (2017) Interleukin-27 Is a Potential Rescue Therapy for Acute Severe Colitis Through Interleukin-10-Dependent, T-Cell-Independent Attenuation of Colonic Mucosal Innate Immune Responses. Inflamm Bowel Dis 23:1983-1995

Showing the most recent 10 out of 21 publications