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Bézie S., L. Boucault, E. Autrusseau, S. Kilens, D. Meistermann, B. Martinet, V. Daguin, A. Donnart, E. Charpentier, L. David, I. Anegon* and C. Guillonneau*.

Year | J. Clin. Invest. Insight. 9;2(3):e90088


Interleukin-34 is a cytokine with only partially understood functions, described for the first time in 2008. Although IL-34 shares very little homology with CSF-1 (CSF1, M-CSF), they share a common receptor CSF-1R (CSF-1R) and IL-34 has also two distinct receptors (PTP-ζ) and CD138 (syndecan-1). To make the situation more com- plex, IL-34 has also been shown as pairing with CSF-1 to form a heterodimer. Until now, studies have demonstrated that this cytokine is released by some tissues that differ to those where CSF-1 is expressed and is involved in the dif- ferentiation and survival of macrophages, monocytes, and dendritic cells in response to inflammation. The involve- ment of IL-34 has been shown in areas as diverse as neu- ronal protection, autoimmune diseases, infection, cancer, and transplantation. Our recent work has demonstrated a new and possible therapeutic role for IL-34 as a Foxp3+ Treg-secreted cytokine mediator of transplant tolerance. In this review, we recapitulate most recent findings on IL-34 and its controversial effects on immune responses and address its immunoregulatory properties and the potential of targeting this cytokine in human.