Figure 7. Treg-specific Ptpn2 haploinsufficiency promotes pathogenic Treg conversion and enhances arthritis severity.

(A) Generation of B6.SKG.H2^d/d.FoxP3^YFP-Cre+/–.tdTom^fl/+.Ptpn2^fl/+ fate-mapping mice. (B) Clinical score and ankle swelling of female B6.SKG.H2^d/d.FoxP3^YFP-Cre+/–.tdTom^fl/+.Ptpn2^+/+ (n = 8) and Ptpn2^fl/+ (n = 8) mice after injection with mannan at 8 weeks of age. (C) IL-17–expressing cells within TCRβ⁺CD4⁺tdTom⁺ cells in lymph nodes (top; axillary and popliteal; Ptpn2^+/+, n = 10; Ptpn2^fl/+, n = 10) and arthritic ankles (bottom; Ptpn2^+/+, n = 8; Ptpn2^fl/+, n = 7). Flow plots represent frequency within the TCRβ⁺CD4⁺tdTom⁺ population. Graphs represent frequency within the total TCRβ⁺CD4⁺ T cell population. (D) Frequency of TCRβ⁺CD4⁺tdTom^– Th17 cells represented as the frequency within the total TCRβ⁺CD4⁺ T cell population in the same mice as in C. (E) Transfer of in vitro–generated Ptpn2^+/+ (n = 3) and Ptpn2^+/– SKG (n = 3) eGFP^– exTregs to female Rag2-KO mice (1.5 × 10⁵ exTregs per mouse). Arthritis was induced 4 days after transfer by mannan injection. Compiled data from at least 3 independent experiments are presented in B–D. Experiment in E was performed once. Each symbol in C and D represents an individual mouse. Arthritis severity was quantified using the area under the curve. Bars represent mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001 by Mann-Whitney (B) or unpaired t test (C and E).