Grant: Operating Grant

Recently, new types of lymphocytes called innate lymphocytes have been discovered. Unlike conventional lymphocytes, which respond to specific antigens and generate antibodies and cell-mediated immunity, innate lymphocytes do not respond to specific antigens. Instead they are activated by small hormone-like proteins called cytokines produced by other cells and they produce their own cytokines, which act on surrounding cells. Innate lymphocytes can be divided into multiple families based on the cytokines they produce. They are mostly found in the gut and lung and serve as a first line of defense against worms, some bacteria and fungi. The production of too much cytokines by innate lymphocytes also causes tissue inflammation, which leads to diseases such as asthma and inflammatory bowel disease. The goal of this study is to find out how innate lymphocytes are generated from stem cells in the bone marrow. Currently, how conventional lymphocytes are generated from bone marrow stem cells is well studied. In contrast, very little is known about how innate lymphocytes are generated. Recently we and others have found the proteins that are critical for the generation of different families of innate lymphocytes. We have also found immature innate lymphocytes in the bone marrow. Based on those previous studies, we now plan to find out how individual families of innate lymphocytes are generated from immature lymphocytes in the bone marrow and how these processes are controlled. Innate lymphocytes have to be continuously produced from immature lymphocytes in the bone marrow. We hope to find a way to control the number of specific family of innate lymphocytes without affecting other lymphocytes. This study may lead to new ways of treating asthma and inflammatory bowel disease.