Table 1.

Foxp3 post-translational modifications (PTM) and mutations accounting for the loss of Treg cell phenotype/function and associated diseases.

Alterations	Foxp3 PTM alterations/mutation domains	Effect	Treg cell-associated defect	Disease	References
Increased serum levels of CCL3	K48-linked polyubiquitination	Foxp3 degradation	Reduced Treg cell function	Psoriasis	(117)
Increased Sirt1 deacetylation	Reduced acetylation	Reduced Foxp3 expression	Impaired Treg cell number and suppressive function	Abdominal aortic aneurysm, Hashimoto's Thyroiditis, Grave's disease	(118–120)
Reduced TIP60 expression	Reduced acetylation	Reduced Foxp3 expression	Imbalanced Th17/Treg cell differentiation; impaired Treg cell proliferation	Rheumatoid arthritis	(121)
Germline mutations	FKH (A384T in Exon 11)	Altered interaction with TIP60	Impaired Treg cell suppressive function; impaired Foxp3 function; reduced Foxp3 stability	IPEX	(122–124)
Germline mutations	PRR (227delT, 303_304delTT in Exon 2)	Altered interaction with RORα and RORγt	Impaired Foxp3 function	IPEX	(125, 126)
Germline mutations	LZ (748_750delAAG, 750_752delGGA in Exon 7)	Impaired Foxp3 dimerization	Impaired Foxp3 function	IPEX	(127)

Chemokine (C-C motif) ligand (CCL)3, sirtuin (Sirt)1, tat-interactive protein 60 kDa (TIP60), forkhead domain (FKH), prolin-rich region (PRR), leucine zipper (LZ), RAR-related orphan receptor (ROR)α, immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX).