Therefore, IL-10 has been shown to synergize with IL-21 to induce the secretion of IgA by CD40L-stimulated human B cells, whereas IL-4 diminished it . The stimulatory signalling through the IL-21R/γc complex, rather than other
γc-containing cytokine receptors, such as those for IL-2 or IL-4 has previously been demonstrated to be very important to induce switching to IgG and IgA . Although this recognized importance, in this study, there were no differences between the mRNA expression of this receptor between periodontitis and healthy individuals. However, although the expression of IL-21R and CD40L were similar between groups, the expression of IL-21 and levels of IL-10 was upregulated in chronic CB-839 nmr periodontitis tissues when compared to healthy ones. In addition, the levels of IL-4 were lower in periodontitis tissues than healthy biopsies. Concomitant with the increased expression of IL-21 and IL-10 and decreased in IL-4 levels in periodontitis tissues; the amounts of salivary IgA were significantly higher
in periodontitis subjects. Together, these data suggest that the abovementioned role of IL-21, IL-10, and IL-4 in Ig isotype switching might also take place in chronic periodontitis and indicate an immunomodulation of the oral mucosal tissues in subjects under periodontal pathogens challenge. The role of these cytokines has been already investigated in periodontitis; however, the majority of the studies have focused on the functions of cytokines on CP-690550 research buy the Th1/Th2 or Th17/Treg responses. In according to the present results, previous studies showed that IL-21 was highly expressed in gingival biopsies of chronic periodontitis  and the levels of IL-21 in gingival crevicular Methane monooxygenase fluid decreased after treatment of chronic periodontitis . Furthermore, our findings confirm previous observations in which lower levels of IL-4 [25, 26] and higher levels of IL-10 [27, 28] were associated with periodontitis. In addition, in agreement with present study, the levels of IgA against different pathogens have been found to be higher in subjects with periodontal disease [3, 4,
6]. Therefore, salivary IgA, the most abundant immunoglobulin isotype in saliva seems to be potentially protective against periodontal pathogens and their virulence factors [6, 29]. Accordingly, the selective IgA primary immunodeficiency (IgAD) predisposes to oral mucosal infections, supporting the role of IgA in inhibiting mucosal colonization and invasion of pathogens , although the loss of IgA did not result in an increase in periodontitis levels in IgAD individuals [30, 31]. In this study, we suggested that the higher amount of the IgA found in the saliva of the chronic periodontitis subjects may have a direct relationship with the higher expression of IL-21 and IL-10 and lower expression of IL-4 in periodontitis tissues.