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Th17 Cells Coordinate with Th22 Cells in Maintaining Homeostasis of Intestinal Tissues and both are Depleted in SIV-Infected Macaques.

Xu H, Wang X, Veazey RS - J AIDS Clin Res (2014)

Bottom Line: Here we compared Th17 and Th22 cells in their phenotype, effector/cytokine function, and frequency in blood and intestinal mucosal tissues, and correlate levels with mucosal damage in SIV-infected rhesus macaques.Further, Th17/Th22 cells display distinct tissue-specific distributions.Both Th17 and Th22 cells and cytokine secretion were significantly depleted in both blood and intestine in chronically SIV-infected macaques.

View Article: PubMed Central - PubMed

Affiliation: Tulane National Primate Research Center, Tulane University School of Medicine, 18703 Three Rivers Road Covington, LA 70433, USA.

ABSTRACT
Th17 and Th22 cells are thought to function as innate regulators of mucosal antimicrobial responses, tissue inflammation and mucosal integrity, yet their role in persistent SIV infection is still unclear. Here we compared Th17 and Th22 cells in their phenotype, effector/cytokine function, and frequency in blood and intestinal mucosal tissues, and correlate levels with mucosal damage in SIV-infected rhesus macaques. We found that Th17/Th22 cells share similar features in that both highly produce TNF-α and IL-2 and express CCR5 in intestinal tissues; yet very few show cytotoxic functions, as evidenced by lack of IFN-γ and granzyme B production. Further, Th17/Th22 cells display distinct tissue-specific distributions. Both Th17 and Th22 cells and cytokine secretion were significantly depleted in both blood and intestine in chronically SIV-infected macaques. The frequency of Th17 and Th22 cells in the intestine positively correlated with percentages of intestinal CD4+ T cells and negatively with damage to intestinal mucosa, and plasma viral loads in SIV infection. These findings indicate Th17 and Th22 cells share considerable functions, and may coordinate in innate mucosal immune responses, and their regional loss in the intestine may be associated with local mucosal immune dysfunction in persistent HIV/SIV infection.

No MeSH data available.


Related in: MedlinePlus

Comparison of blood and intestinal IL-17+IL-22-, IL-17+IL-22+ or IL-17-IL-22+ CD4 T cell subsets in chronic SIV infection of macaquesPercentages of IL-17+IL-22-, IL-17+IL-22+ or IL-17-IL-22+ cell subsets in peripheral blood and intestinal mucosal tissues in uninfected (Blood, n=21; Jejunum, n=42) and chronically SIV-infected (Blood, n=15; Jejunum, n=16) macaques are shown. Statistical analyses show significant differences in levels of IL-17+IL-22-, IL-17+IL-22+ or IL-17-IL-22+ cells in blood and intestine between SIV-infected and uninfected animals.
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Figure 4: Comparison of blood and intestinal IL-17+IL-22-, IL-17+IL-22+ or IL-17-IL-22+ CD4 T cell subsets in chronic SIV infection of macaquesPercentages of IL-17+IL-22-, IL-17+IL-22+ or IL-17-IL-22+ cell subsets in peripheral blood and intestinal mucosal tissues in uninfected (Blood, n=21; Jejunum, n=42) and chronically SIV-infected (Blood, n=15; Jejunum, n=16) macaques are shown. Statistical analyses show significant differences in levels of IL-17+IL-22-, IL-17+IL-22+ or IL-17-IL-22+ cells in blood and intestine between SIV-infected and uninfected animals.

Mentions: To investigate the effects of persistent SIV infection on Th17/Th22 cell subsets in rhesus macaques, we examined their changes in peripheral blood and jejunum. In normal, healthy animals, the frequency of Th17 and Th22 cells were similar in blood (1.98% vs. 2.07%, respectively) (Figure 3A and 3C), but levels of Th17 cells were significantly higher than Th22 cells in jejunum (6.85% vs. 3.43%, p<0.0001) (Figure 3B and 3D). There was also a substantial reduction in frequency of both Th17 and Th22 cells in the peripheral blood and intestinal mucosal tissues in chronically SIV-infected animals, compared with uninfected controls (p<0.001) (Figure 3). As shown in Figure 4, all Th17/Th22 cell subsets in blood and mucosal tissues were significantly depleted in persistent SIV infection. Thus, despite distinct differences in cytokine production, both subsets are depleted, resulting in loss of the major sources of both IL-17 and IL-22 in tissues, which likely contributes to the pathogenesis of HIV/SIV infection.


Th17 Cells Coordinate with Th22 Cells in Maintaining Homeostasis of Intestinal Tissues and both are Depleted in SIV-Infected Macaques.

Xu H, Wang X, Veazey RS - J AIDS Clin Res (2014)

Comparison of blood and intestinal IL-17+IL-22-, IL-17+IL-22+ or IL-17-IL-22+ CD4 T cell subsets in chronic SIV infection of macaquesPercentages of IL-17+IL-22-, IL-17+IL-22+ or IL-17-IL-22+ cell subsets in peripheral blood and intestinal mucosal tissues in uninfected (Blood, n=21; Jejunum, n=42) and chronically SIV-infected (Blood, n=15; Jejunum, n=16) macaques are shown. Statistical analyses show significant differences in levels of IL-17+IL-22-, IL-17+IL-22+ or IL-17-IL-22+ cells in blood and intestine between SIV-infected and uninfected animals.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4215515&req=5

Figure 4: Comparison of blood and intestinal IL-17+IL-22-, IL-17+IL-22+ or IL-17-IL-22+ CD4 T cell subsets in chronic SIV infection of macaquesPercentages of IL-17+IL-22-, IL-17+IL-22+ or IL-17-IL-22+ cell subsets in peripheral blood and intestinal mucosal tissues in uninfected (Blood, n=21; Jejunum, n=42) and chronically SIV-infected (Blood, n=15; Jejunum, n=16) macaques are shown. Statistical analyses show significant differences in levels of IL-17+IL-22-, IL-17+IL-22+ or IL-17-IL-22+ cells in blood and intestine between SIV-infected and uninfected animals.
Mentions: To investigate the effects of persistent SIV infection on Th17/Th22 cell subsets in rhesus macaques, we examined their changes in peripheral blood and jejunum. In normal, healthy animals, the frequency of Th17 and Th22 cells were similar in blood (1.98% vs. 2.07%, respectively) (Figure 3A and 3C), but levels of Th17 cells were significantly higher than Th22 cells in jejunum (6.85% vs. 3.43%, p<0.0001) (Figure 3B and 3D). There was also a substantial reduction in frequency of both Th17 and Th22 cells in the peripheral blood and intestinal mucosal tissues in chronically SIV-infected animals, compared with uninfected controls (p<0.001) (Figure 3). As shown in Figure 4, all Th17/Th22 cell subsets in blood and mucosal tissues were significantly depleted in persistent SIV infection. Thus, despite distinct differences in cytokine production, both subsets are depleted, resulting in loss of the major sources of both IL-17 and IL-22 in tissues, which likely contributes to the pathogenesis of HIV/SIV infection.

Bottom Line: Here we compared Th17 and Th22 cells in their phenotype, effector/cytokine function, and frequency in blood and intestinal mucosal tissues, and correlate levels with mucosal damage in SIV-infected rhesus macaques.Further, Th17/Th22 cells display distinct tissue-specific distributions.Both Th17 and Th22 cells and cytokine secretion were significantly depleted in both blood and intestine in chronically SIV-infected macaques.

View Article: PubMed Central - PubMed

Affiliation: Tulane National Primate Research Center, Tulane University School of Medicine, 18703 Three Rivers Road Covington, LA 70433, USA.

ABSTRACT
Th17 and Th22 cells are thought to function as innate regulators of mucosal antimicrobial responses, tissue inflammation and mucosal integrity, yet their role in persistent SIV infection is still unclear. Here we compared Th17 and Th22 cells in their phenotype, effector/cytokine function, and frequency in blood and intestinal mucosal tissues, and correlate levels with mucosal damage in SIV-infected rhesus macaques. We found that Th17/Th22 cells share similar features in that both highly produce TNF-α and IL-2 and express CCR5 in intestinal tissues; yet very few show cytotoxic functions, as evidenced by lack of IFN-γ and granzyme B production. Further, Th17/Th22 cells display distinct tissue-specific distributions. Both Th17 and Th22 cells and cytokine secretion were significantly depleted in both blood and intestine in chronically SIV-infected macaques. The frequency of Th17 and Th22 cells in the intestine positively correlated with percentages of intestinal CD4+ T cells and negatively with damage to intestinal mucosa, and plasma viral loads in SIV infection. These findings indicate Th17 and Th22 cells share considerable functions, and may coordinate in innate mucosal immune responses, and their regional loss in the intestine may be associated with local mucosal immune dysfunction in persistent HIV/SIV infection.

No MeSH data available.


Related in: MedlinePlus