Deletion and pharmacologic targeting of HDAC2, HDAC7, HDAC9, HDAC6, HDAC10, HDAC11, as well as Sirtuin-1 (Sirt1) improves Treg function. Of those, HDAC6 is the most promising candidate since HDAC6 knockout mice are normal, and HDAC6 selective pharmacologic inhibitors are being tested in clinical trials for other indications. Domain color codes: Red, classic Zn2+ dependent HDAC catalytic domain; Pink, class IIa HDAC catalytic domain (histidine to tyrosine substitution compared to class I, IIb, and IV HDAC); orange, NAD+ dependent class III HDAC (Sirtuin) catalytic domain; black, inactive leucine rich domain (HDAC10); purple, nuclear localization sequence; brown, mitochondrial targeting sequence; yellow, MEF2 binding site. Abbreviations: N, nucleus; C, cytoplasm; M, mitochondria.