Influence of CD137L Reverse Signaling on Myelopoiesis in Acute and Chronic Inflammation

Abstract

CD137 is a costimulatory molecule expressed on activated T cells. The signaling of CD137 into T cells upon ligation by its ligand, CD137L expressed on antigen presenting cells (APC), can potently enhance the activation of T cells. Reversibly CD137 can also induce signalling into APC via CD137L to promote activation and proliferation. By investigating the role of CD137L on myelopoiesis under inflammatory condition in vitro and in vivo, it was shown that CD137L reverse signaling represents a novel and potent growth and differentiating factor for murine myeloid cells during acute and chronic inflammation. In acute peritonitis and chronic aging model CD137L reverse signaling promotes myeloid cell proliferation and accumulation. Further investigations revealed the driving force behind the observed myelopoiesis as CD137+CD4+ T cells and absence of CD137L reverse signaling leads to accumulation of undifferentiated progenitor cells.