T Regulatory and T Helper 17 Cells in Primary Sjögren’s Syndrome: Facts and Perspectives

Table 1

Indicators of Treg cell and IL-17/IL-17-producing T cell involvement in primary Sjögren’s syndrome.

Source	Observation	References
Salivary glands	FoxP3 expression is associated with the severity of glandular inflammation; Inverse relationship between glandular and circulating FoxP3+ cells; Lower FoxP3+ cells correlate with adverse predictors for lymphoma development; CD25low/-GITR+ T cells are present in mononuclear cell infiltrate; High expression of IL-17 and IL-17R; High expression of IL-6, IL-21, IL-22, and IL-23; CD4+, CD8+, mast cells, and DN T cells produce IL-17; IL-17 is associated with the severity of glandular damage; DN T cells are associated with GCs	[21, 23]; [21]; [21]; [26]; [50–52]; [50, 52–57]; [55, 60, 61]; [51, 52]; [61]
Saliva/tears	Increased levels of IL-17 in saliva; Increased levels of IL-17 in tears; No association between salivary IL-17 and glandular damage	[64]; [65–67]; [64]
Serum	Increased levels of IL-17; Increased levels of IL-6, IL-21, and IL-23; IL-17 prevalence is dependent on disease duration; Serum IL-17 is higher in patients with MSG-GCs	[50, 51, 69, 70]; [52, 53]; [70]; [69]
Peripheral blood	Altered Treg cell percentage (increased, decreased, or comparable percentages with; respect to HD); Inverse correlation between the percentage of Treg cells and CRP, ESR, RF, and IgG; No differences in Treg cell percentage according to ESSDAI and SSDAI; Expansion of functionally suppressive CD25low/-GITR+T cells; Suppressive CD25low/-GITR+T cell percentage are expanded in inactive pSS; Increase of circulating CD4+Th17 cells; Increase of circulating IL-17+DN T cells	[17–26]; [19]; [25, 26]; [26]; [26]; [26]; [51, 59–61]; [60, 61]
Intrinsic cell abnormalities	The Vbeta repertoire of pSS Treg cells is polyclonal and not significantly restricted as compared with that in controls; IL-17-producing DN T cells are totally insensitive to dexamethasone in vitro; IL-17A gene displays an association with GC status	[17]; [60]; [91]

Treg = T regulatory cells; IL = interleukin; Th17 = IL-17-producing T helper cells; FoxP3 = Forkhead box protein P3; GITR = glucocorticoid-induced tumor necrosis factor receptor related protein; DN = IL-17-producing double negative T cells; GC = germinal center; CRP = C reactive protein; ESR = erythrocyte sedimentation rate; RF = rheumatoid factor; IgG = immunoglobulin G; ESSDAI = EULAR Sjögren’s syndrome disease activity index; SSDAI = Sjögren’s syndrome disease activity index; and HD = healthy donors.