| Autor: |
Antoine Freuchet, Apolline Salama, Séverine Bézie, Laurent Tesson, Séverine Rémy, Romain Humeau, Hadrien Règue, Léa Flippe, Pärt Peterson, Nadège Vimond, Claire Usal, Séverine Ménoret, Jean-Marie Heslan, Franck Duteille, Frédéric Blanchard, Magali Giral, Marco Colonna, Ignacio Anegon, Carole Guillonneau |
| Rok vydání: |
2022 |
| DOI: |
10.1101/2022.02.04.479184 |
| Popis: |
Immune homeostasis requires fully functional Tregs with a stable phenotype to control autoimmunity. Although IL-34 is a cytokine first described as mainly involved in monocyte cell survival and differentiation, we recently described its expression by CD8+ Tregs in a rat model of transplantation tolerance and by activated FOXP3+ CD4+ and CD8+ Tregs in human healthy individuals. However, its role in autoimmunity and potential in human diseases remain to be determined. Here we report that the absence of expression of IL-34 in Il34-/- rodents leads to an unstable phenotype, with production of multiple auto-antibodies, exacerbated under inflammatory conditions with increased susceptibility to DSS- and TNBS-colitis in deficient animals. Moreover, we strikingly revealed the inability of Il34-/- CD4+ Tregs to protect Il2rg-/- rats from a wasting disease induced by transfer of pathogenic cells, in contrast to Il34+/+ CD4+ Tregs. We also showed that IL-34 treatment delayed EAE in mice as well as GVHD and human skin allograft rejection in immune humanized immunodeficient NSG mice. Finally, we show that presence of IL-34 in the serum is associated with a longer rejection-free period in kidney transplanted patients. Altogether, our data emphasize on the crucial necessity of IL-34 for immune homeostasis and for CD4+ Tregs suppressive function. Our data also shows the therapeutic potential of IL-34 in human transplantation and auto-immunity. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
