Increased CD4⁺CD45RA^-FoxP3^low cells alter the balance between Treg and Th17 cells in colitis mice

To investigate the role of regulatory T cell (Treg) subsets in the balance between Treg and T helper 17 (Th17) cells in various tissues from mice with dextran sulfate sodium-induced colitis.

Treg cells, Treg cell subsets, Th17 cells, and CD4⁺CD25⁺FoxP3⁺IL-17⁺ cells from the lamina propria of colon (LPC) and other ulcerative colitis (UC) mouse tissues were evaluated by flow cytometry. Forkhead box protein 3 (FoxP3), interleukin 17A (IL-17A), and RORC mRNA levels were assessed by real-time PCR, while interleukin-10 (IL-10) and IL-17A levels were detected with a Cytometric Beads Array.

In peripheral blood monocytes (PBMC), mesenteric lymph node (MLN), lamina propria of jejunum (LPJ) and LPC from UC mice, Treg cell numbers were increased (P < 0.05), and FoxP3 and IL-10 mRNA levels were decreased. Th17 cell numbers were also increased in PBMC and LPC, as were IL-17A levels in PBMC, LPJ, and serum. The number of FrI subset cells (CD4⁺CD45RA⁺FoxP3^low) was increased in the spleen, MLN, LPJ, and LPC. FrII subset cells (CD4⁺CD45RA^-FoxP3^high) were decreased among PBMC, MLN, LPJ, and LPC, but the number of FrIII cells (CD4⁺CD45RA^-FoxP3^low) and CD4⁺CD25⁺FoxP3⁺IL-17A⁺ cells was increased. FoxP3 mRNA levels in CD4⁺CD45RA^-FoxP3^low cells decreased in PBMC, MLN, LPJ, and LPC in UC mice, while IL-17A and RORC mRNA increased. In UC mice the distribution of Treg, Th17 cells, CD4⁺CD45RA^-FoxP3^high, and CD4⁺CD45RA^-FoxP3^low cells was higher in LPC relative to other tissues.

Increased numbers of CD4⁺CD45RA^-FoxP3^low cells may cause an imbalance between Treg and Th17 cells that is mainly localized to the LPC rather than secondary lymphoid tissues.