CESTI-IHU: Dendritic cells and IL-22BP: targets for an innovative immunotherapeutic strategy

3 April 2017

Dendritic cells and IL-22BP: targets for an innovative immunotherapeutic strategy for the treatment of inflammatory diseases

Within the 1064 INSERM Transplantation and Immunology Research Center (CRTI INSERM 1064 ) and supported by the CESTI IHU, Professor Régis Josien and his team are particularly interested in dendritic cells. These cells are central sentinels of the immune system and play a major role in the development of new immuno-therapeutic strategies for the treatment of organ transplant rejection as well as inflammatory and autoimmune diseases.

One of the original functions of these dendritic cells is their ability to produce IL-22BP, a soluble receptor inhibiting interleukin-22. Secreted by the immune system, interleukin-22 participates in the dialogue between cells, notably at the level of the intestine, liver or skin. “Why does interleukin-22 require fine action regulation by an inhibitory receptor? This is what we have sought to understand”, says Professor Josien.

After demonstrating that IL-22BP is produced by a well defined population of dendritic cells, particularly at the level of the intestinal mucosa, the creation of IL-22BP-deficient animals has made it possible to understand the role of this molecule in inflammatory diseases where IL-22 is involved. Thus, in the chronic inflammatory bowel diseases (IBD, Crohn’s disease and hemorrhagic recto colitis), IL-22BP has a major protective role. On the contrary, in psoriasis its role is harmful. This IL-22 functional duality explains the need for regulation and this regulation is carried out by some dendritic cells.

“These results have allowed us to initiate a more ambitious research program in IBD with the hypothesis that blocking IL-22BP could have potential therapeutic value. This hypothesis is currently being tested with new support from the Francois Aupetit Association and the European Crohn and Colitis Organization, which demonstrates the important leverage effect of the original CESTI-IHU program. Its action was crucial to initiate and develop this innovative project”

The results of this work have been the subject of several scientific publications in two international peer-reviewed journals.

1- Martin JC, Wolk K, Beriou G, Abidi A, Witte-Händel E, Louvet C, Kokolakis G, Drujont L, Dumoutier L, Renauld JC, Sabat, R, Josien R. Limited presence of IL-22 binding protein, a natural IL-22 inhibitor, strengthens psoriatic skin inflammation. J. Immunol 2017. In press.
2- Martin JC, Bériou G, Heslan M, Bossard C, Jarry A, Abidi A, Hulin P, Ménoret S, Thinard R, Anegon I, Jacqueline C, Lardeux B, Halary F, Renauld JC, Bourreille A, Josien R. IL-22BP is produced by eosinophils in human gut and blocks IL-22 protective actions during colitis. Mucosal Immunol. 2016. 220:692-700. doi: 10.1038/mi.2015.83.
3- Martin J, Bériou G, Heslan M, Chauvin C, Utriainen L, Aumeunier A, Scott C.L, Mowat A, Cerovic V, Houston S.A, Leboeuf M, Hubert F.X, Hémont C, Merad M, Milling S, and Josien R. Interleukin-22 binding protein (IL-22BP) is constitutively expressed by a subset of conventional dendritic cells and is strongly induced by retinoic acid. Mucosal Immunol. 2014, 7:101-113