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Volume 11, Pages 2011-2019
Review Article

The Role of CD40/CD40 Ligand Interactions in Bone Marrow Granulopoiesis

1Department of Hematology, University of Crete School of Medicine, P.O. Box 1352, 71110 Heraklion, Crete, Greece
2Graduate Program “Molecular Basis of Human Disease”, University of Crete School of Medicine, 71003 Heraklion, Greece

Received 29 August 2011; Accepted 5 October 2011

Academic Editor: Marco Antonio Cassatella

Copyright © 2011 Irene Mavroudi and Helen A. Papadaki. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The CD40 ligand (CD40L) and CD40 are two molecules belonging to the TNF/TNF receptor superfamily, and their role in adaptive immune system has widely been explored. However, the wide range of expression of these molecules on hematopoietic as well as nonhematopoietic cells has revealed multiple functions of the CD40/CD40L interactions on different cell types and processes such as granulopoiesis. CD40 triggering on stromal cells has been documented to enhance the expression of granulopoiesis growth factors such as granulocyte-colony-stimulating factor (G-CSF) and granulocyte/monocyte-colony-stimulating factor (GM-CSF), and upon disruption of the CD40/CD40L-signaling pathway, as in the case of X-linked hyperimmunoglobulin M (IgM) syndrome (XHIGM), it can lead to neutropenia. In chronic idiopathic neutropenia (CIN) of adults, however, under the influence of an inflammatory microenvironment, CD40L plays a role in granulocytic progenitor cell depletion, providing thus a pathogenetic cause of CIN.