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Thus, the tumor microenvironment in Apc/Min+ mice have markedly increased numbers of Foxp3+ Tregs but only moderately increased IL-17A+ CD4 T cells in the LP, suggesting that Apc/Min+ Foxp3+ Tregs are altered in the LP. Figure 2 Th17 cells and altered Foxp3+ Tregs cells are both increased in the lamina propria of Apc/Min+ mice. (a�Cd) Four-month-old ApcMin/+ mice and their littermate controls (n = 3 for each group) were sacrificed. Single cell suspensions of LP cells were ... We further examined possible alterations in Apc/Min+ Foxp3+ Treg. It has been reported that Gata-3 is a critical transcription factor needed to maintain Treg function in vivo [6]. In addition, it has been shown that Gata-3 is required for IL-10 expression and IL-10 is critical for inhibiting intestinal polyposis [14, 23]. As endogenous Apc/Min+ Treg in the LP clearly failed to regress tumors, we tested whether these expanded Treg stably express Gata-3. Interestingly, the percentage of the Gata-3-Foxp3+ Apc/Min+ Treg population markedly increased in the LP (8.82% versus 29%) (Figure 2(c)). However, the absolute number of Foxp3+Gata-3+ Tregs was also increased in Apc/Min+ mice. This suggests that the expansion of Gata-3-Apc/Min+ Treg was more favored by the tumor microenvironment, giving more Telomerase nonfunctional Treg. It has been shown that Helios, a member of the Ikaros family, is expressed in more mature and proliferating CD4 T cells and Treg as well as in thymic-derived Tregs [24�C26]. We also showed that the frequency of Helios+ Foxp3+ Treg was markedly increased in Apc/Min+ mice while Helios-Foxp3+ Treg were very low (Figure 2(d)). Interestingly, Helios+ cells were not increased in the CD4 effector population, suggesting that the tumor microenvironment favors the activation and proliferation of Apc/Min+ Treg. Taken together, our results show that Apc/Min+ Foxp3+ Tregs undergo robust expansion in the intestinal tumor microenvironment and these Treg have altered Gata-3 expression that is important for Treg function in vivo. 3.3. The Heterozygous Apc Gene Mutation in Treg Alone Does Not Impair Treg-Mediated Control of Intestinal Tumorigenesis Next we questioned whether the heterozygous mutation of Apc gene in Treg is responsible for their dysfunction in intestinal tumorigenesis. It has been known that Apc/Min+ mice display thymic atrophy and altered bone marrow subpopulations. Transplantation of wild type bone marrow into Apc/Min+ mice does not correct these phenotypes; thus the developmental environment of immune cells is altered [21]. It has been demonstrated that adoptive transfer of wild type Treg could effectively inhibit intestinal tumorigenesis [14].