In this Review, the authors explain how post-translational protein modification by the small ubiquitin-like modifier (SUMO) family is emerging as an important regulator of immune cell function. Notably, inhibition of sumoylation is showing promise as a cancer therapy and may also have therapeutic use in various autoimmune conditions.

New immunotherapies have the potential to mediate a sustained remission from certain autoimmune diseases. This has been referred to as achieving an ‘immune reset’ in patients. Here, Junt and colleagues discuss how we can most accurately define the term immune reset and explain the challenges in identifying suitable biomarkers of long-term disease remission.

This Progress article describes recent studies showing that the human lipopolysaccharide sensor caspase-4 activates pro-IL-18 and causes vascular leakage by inducing pyroptosis in endothelial cells. Structural studies have uncovered allosteric sites of caspase-4 that might be effective drug targets to inhibit vascular leakage.

HIV infection persists under antiretroviral therapy due to a reservoir of latently infected cells. This Perspective discusses how host immune responses might affect the establishment and persistence of the viral reservoir, an understanding of which supports the development of immune-based approaches to ‘cure’ HIV infection by disrupting the reservoir.