Figure 1.

Pharmacodynamic activity of pMHCII-NPs. pMHCII-NPs target autoantigen-experienced CD4+ T cells and induce their differentiation into memory TR1-like cells followed by their systemic expansion. This process involves IFN-γ and IL-10 signaling, but does not require IL-27. pMHCII-NP-induced TR1-like cells carry out their regulatory function by suppressing other autoreactive T-cell specificities via IL-10, IL-21 and TGF-β. IL-10 and TGF-β have immunosuppressive effects on autoantigen-loaded APCs, inhibiting their proinflammatory function and thus avoiding the activation of other non-cognate autoreactive T cells. pMHCII-NP-induced TR1-like cells can also interact with cognate B-cells, promoting their differentiation into Bregs in part via IL-21. Figure adapted from Clemente-Casares et al. (11).