T Cell-Derived GM-CSF, Regulation of Expression and Function

Granulocyte-macrophage colony-stimulating factor (GM-CSF), also known as colony stimulating factor 2 (CSF2), was termed due to its ability to promote in vitro differentiation of granulocytic and macrophage colonies from bone marrow precursors and is therefore considered as a hematopoietic-cell growth factor. However, GM-CSF-null mice undergo normal hematopoiesis and only the maturation of alveolar macrophages is compromised. GM-CSF is produced by various types of cells, including activated T/B cells, monocytes/macrophages, neutrophils, fibroblasts, epithelial cells, endothelial cells, stromal cells and tumor cells.

An increasing body of evidences supports GM-CSF as a potent proinflammatory factor that is critically involved in inflammatory and autoimmune conditions and that the function of this cytokine varies depending on the origin of the cytokine and the status of the cells in vivo. CD4+ T cells are critical for immune response against microbial infection but also play essential roles in autoimmunity. Naïve CD4+ T cells can differentiate into various subsets of T helper (TH) cells including TH1, TH2 and TH17 cells.

Each subset of TH cells expresses unique cytokines and has distinct functions in immunity. Interestingly, GM-CSF is more or less expressed by all of these TH cells. In this review, we will focus on the recent discoveries concerning the function of CD4+ T cell-derived GM-CSF as well as the regulatory mechanism governing GM-CSF expression by CD4+ T cells.

Read More