IL-7 receptor blockade in human PBMC

Targeting the expansion and survival of pathogenic memory immune cells is a promising therapy to prevent chronic autoimmune attacks. Interleukin-7 receptor a chain (IL-7Ra) genetic variation were repeatedly associated with susceptibility of several chronic autoimmune and inflammatory diseases. Interleukin-7 (IL-7) is as a critical survival factor for the maintenance of mature T lymphocytes and numerous studies in rodent suggest targeting the IL-7/IL-7Ra pathway holds promise for the treatment of autoimmune diseases or transplant rejection. In this study, we evaluated agonist and antagonist properties of different anti-IL7Ra mAbs recognizing different type of epitope. To determine if agonist/antagonist anti-IL7Ra mAbs could deliver effective agonist signals capable of modifying human T cells, we analyzed by RNA-based-next-generation sequencing (RNA-SEQ) the transcriptome of human PBMC incubated during 3,5 hours with a site-1 (IgG4 #1 or IgG1 #2) or site-1/2b (IgG4) mAbs in the presence or not of exogenous human IL-7 (5 ng/ml). Altogether, transcriptional analysis confirmed that, while site-1 and site-1/2b anti-human IL-7Ra mAbs shared similar antagonist properties, the two site-1 mAbs induced significant human PBMC transcriptional modification compatible with T-cell activation and inflammatory responses associated by the MAPK/ERK pathway. Overall design: Human PBMC from seven independant healthy volunteers were incubated during 3,5 hours with a site-1 (IgG4 #1 or IgG1 #2) or site-1/2b (IgG4) mAbs in the presence or not of exogenous human IL-7 (5 ng/ml).