Figure 6. Silencing the IL-23R-STAT3 Axis Rescues the Blimp1-Deficient T_Fr Phenotype.

(A) Schematic presentation of experimental protocol. KO Treg cells were sorted and cultured withanti-CD3andanti-CD28 plusIL-2for3days. Cells were infected with lentivirus expressing the Thy1.1 reporter plus IL-23R-shRNA or Ctrl-shRNA. On day 4, sorted Thy1.1⁺ Treg along with CD45.1⁺ naive CD4⁺ T cells were transferred into Tcra^−/− hosts followed by immunization with NP-OVA in CFA on day 11. Splenocytes were analyzed on day 20.

(B) Thy1.1⁺ T_FR, CD45.2⁻ Thy1.1⁻ T_FH and GL7⁺ B cells, IL-17A, and IFNγ production by Thy1.1⁺ T_FR.

(C) Frequency of CD45.2⁻ Thy1.1⁻ T_FH, Bcl6⁺ IL-17A⁺, and Bcl6⁺ IFNγ⁺ in donor Thy1.1⁺ T_FR cells and in anti-NP IgG titers.

(D–F) WT, KO, Stat3^fl/+Prdm1^fl/flFoxP3^Cre (Stat3^fl/+ + KO), and Stat3^fl/flPrdm1^fl/flFoxP3^Cre (Stat3^fl/fl + KO) mice were analyzed 10 days post-immunization with NP-OVA in CFA.

(D) Splenic T_FR, T_FH, GC B cells, and Bcl6+IL-17A⁺ in Treg.

(E) Frequency of T_FR and Bcl6⁺IL-17A⁺ in Treg and in serum anti-NP IgG titers.

(F) FoxP3 expression in T_FR by the indicated mouse strains.

In (A)–(C), the data represent one of two experiments (C: n = 4/group). In (D)–(F), the results are pooled from two independent experiments (E, n = 4–9/group). *p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001 (unpaired two-tailed Student’s t test). Error bars indicate means ± SEMs.

See also Figure S5.