IL‐34 deficiency impairs FOXP3⁺ Treg function in a model of autoimmune colitis and decreases immune tolerance homeostasis

Abstract

The impact of an IL-34 deficiency at steady state, upon challenges and its use as a therapeutic tool.

Commentary on IL‐34 deficiency impairs FOXP3+ Treg function and decreases immune tolerance homeostasis

“…In addition, IL‐34 promotes transplant tolerance 5 . This justifies the current work of Freuchet et al 3 . that studies three different aspects of IL‐34, that is its role in autoimmune responses, its therapeutic potential and its role as a new biomarker to predict kidney graft survival (Figure 1).…”

“…The second observation is that IL‐34 is another drug candidate to prevent graft or host rejection, as demonstrated in xenogeneic skin graft transplantation or graft‐versus‐host disease (GvHD) (Figure 1). However, IL‐34 should be associated with suboptimal doses of rapamycin 3 . This supports again the importance of Treg, as rapamycin has been shown to spare and potentiate Treg in contrast to calcineurin inhibitors 10 .…”

“… A summary of the main results obtained by Freuchet et al 3 . This cartoon illustrates the three role of IL‐34 evaluated by the authors, namely its role in pathophysiology, as a new treatment or biomarker.…”

“…Several suppressive mechanisms explain the regulatory role of Treg subsets, including cellular lysis and metabolic perturbations of effector T cells, as well as the release of immunosuppressive cytokines. 1 Freuchet et al 3 proposed to evaluate the role of the cytokine IL-34 expressed by Treg subsets in rats and mice. First described to regulate myeloid cell survival and differentiation, 4 IL-34 is also expressed by rat CD8 + Treg, as well as human-activated FOXP3 + CD4 + Treg and CD8 + Treg.…”

“…8 Freuchet et al confirmed that IL-34-deficient rats show a decrease of microglia in the hippocampus. 3 In addition to its role on TRM, CSFR-1 is also involved in monocyte differentiation and macrophage polarization. Again, CSF-1 and IL-34 exhibit the same ability to induce monocyte differentiation and are redundant.…”