SOCS2/ mice have increased susceptibility to allergic airway inflammation Given the marked predisposition of SOCS2/ mice to AD, we investigated whether SOCS2 deficiency resulted in an in- creased response to OVA-induced allergic airway inflammation. SOCS2/ and WT mice were OVA challenged systemically and by aerosol to evoke airway inflammation and airway hyper-responsiveness (AHR). In the absence of allergen chal- lenge, AHR, determined by lung resistance (RL), was not induced in PBS-treated SOCS2/ mice, with these mice having RL values comparable to those of PBS-treated WT 1526 Figure 3. Increased allergic lung inflamma- tion in SOCS2/ mice. (A) Methacholine- induced RL in PBS or OVA-sensitized SOCS2/ and WT mice (n = 7 mice per group). (B) Repre- sentative image of lung sections from each group stained with periodic acid-Schiff stain (bars, 50 µm). (C) Levels of total and OVA- specific IgE in serum of mice from each group. (D) Cells from mediastinal LN were restimulated in triplicates with media or anti-CD3 and anti- CD28 and cytokine secretion was measured by ELISA. (E and F) RAG-1/ mice were reconsti- tuted with PBS as control or with sorted CD4+ T cells isolated from OTII or SOCS2/ OTII mice. The number of mice per group of reconstituted RAG-1/ mice was between five and nine. The mice were then sensitized and challenged with OVA and methacholine-induced RL was mea- sured (E). The cytokine concentrations in the lungs were measured after homogenization (F). Data are from three independent experiments and are presented as the mean and SEM per group. *, P < 0.05; **, P < 0.01; ***, P < 0.001. mice in response to methacholine chal- lenge (Fig. 3 A). In comparison, OVA- sensitized SOCS2/ mice had a striking dose-dependent increase in RL, relative to OVA-sensitized WT animals, that was statistically significant (P < 0.01) at higher methacholine doses (Fig. 3 A). Histological analysis of lungs of OVA- sensitized mice showed more marked inflammation in SOCS2/ mice rela- tive to WT, with peribronchial infil- trating eosinophils and goblet cell hyperplasia (Fig. 3 B). Consistent with a greater allergen-specific type 2 response, OVA-sensitized SOCS2/ mice had significantly enhanced levels of both total IgE (P < 0.05) and OVA-specific IgE (P < 0.001) compared with OVA- treated WT animals (Fig. 3 C). Fur- thermore, cells from the lung-draining mediastinal LN from OVA-sensitized SOCS2/ mice had significantly (P < 0.05) greater production of type 2, but not type 1, cytokines relative to allergen-sensitized WT animals (Fig. 3 D). Again, we observed a significant reduction (P < 0.05) in IL-17 pro- duction in response to antigen challenge in T cells from SOCS2/ mice (Fig. 3 D). To formally determine that the enhanced allergen-induced lung inflammation in SOCS2- deficient mice (Fig. 3, A–D) was attributed to specific altera- tions in CD4+ cell function, we generated SOCS2/xOT/II mice. RAG-1/ mice were reconstituted either with CD4+ T cells from SOCS2/xOT/II or OT/II mice. Recipients were then sensitized and challenged as previously described SOCS2 regulates Th2 responses | Knosp et al.