Effect of NK cells activation in experimental endometriosis

• Grant number: 12/05791-3
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: May 01, 2012
• End date: April 30, 2013
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Rui Alberto Ferriani
• Grantee: Mary Lourdes Lima de Souza Montenegro
• Supervisor: Per H. Basse
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: University of Pittsburgh (Pitt), United States
• Associated to the scholarship: 10/08112-4 - Influence of aerobic exercise on endometriosis induced in rat., BP.PD

Abstract

Endometriosis is an estrogen-dependent gynecologic disease that affects 10-15% women of reproductive age. The etiology of endometriosis remains to be understood, but there is increasing evidence that the immune system plays an important role in its development. It has been suggested that natural killers (NK) cells, an important component of the innate immune system, are decreased in the peritoneal fluid. This atypical behavior of NK cells could facilitate, at least in part, the development of endometriosis. On the other hand, NK cells have a general ability to recognize and kill stressed cells such as virus infected and cancerous cells. This ability can be further enhanced by activation of the NK cells with cytokines such as interleukin-2 (IL-2) and with TLR-ligands such as double-stranded RNA (PolyI:C). Activated NK have been shown to efficiently kill cancer cells both in vitro and in vivo. Here, we suggest the possibility that activated NK cells can be used in treatment of endometrioses as well. Comparable to cancer cells, ectopic endometrial cells are able to adhere, infiltrate and proliferate. However, no previous study has evaluated if activated NK cells can be useful in the control of endometriosis. Therefore, the main aim of this study is to evaluate the effect of activated NK cells against the development and progression of experimental endometriosis. We will use a sophisticated experimental model of endometriosis (based on luciferase-expressing transgenic mice) enabling us to non-invasively follow the development of the endometrial lesions in treated and non-treated animals in real time. Using other fluorescence approaches (immunofluorescence labeling, labeling of NK cells with fluorescent dyes), we also will evaluate the accumulation of endogenously activated NK cells as well as adoptively transferred, IL-2-activated NK cells into endometrial lesions. The results of this project may lead to the development a new and more effective approach for treatment and management of endometriosis. (AU)