The IL4I1 group (Flavia Castellano & Valérie Molinier-Frenkel), on the cover of the last European Journal of Immunology!

Flavia Castellano and Valérie Molinier-Frenkel’s group of team 9 (P. Gaulard) with the collaboration of Xavier Decrouy of PL Imaging and Emmanuel Donnadieu of the Cochin Institute has just published an article on the focused secretion of the IL4I1 enzyme at the immune synapse level and its consequences on the activation of T* lymphocytes. One of the immunofluorescence images showing this secretion by lymphoblastoid lines, which naturally express the enzyme, is illustrated on the inside cover page of the European Journal of Immunology, Vol. 48, Issue 1, January 2018, pages 106-119.

The enzyme IL4I1, secreted by antigen-presenting cells, inhibits the proliferation of effector T lymphocytes and facilitates the development of regulatory T lymphocytes. Its expression by macrophages of various human tumours could affect the patient’s prognosis, as IL4I1 facilitates tumor evasion at the anti-tumour T-response in murine models. The enzyme activity of IL4I1 appears to be partly responsible for its immunosuppressive action, although the molecular mechanisms at work remain imperfectly defined. Here, we show that the presence of IL4I1 during T-cell activation decreases early signalling downstream of the TCR, leading to a global inhibition of T-cells. This effect is more pronounced when there is costimulation via the CD28 molecule. Surprisingly, neither the enzyme reaction products nor the consumption of its amino acid substrate, phenylalanine – essential for lymphocyte proliferation – appear to be involved. The focused secretion of IL4I1 in the synaptic space and its binding to CD3+ lymphocytes could play an important role in the mechanism of action of this immunosuppressive enzyme.