Fig.1 Analysis of hIL4 expression in serum by ELISA. The homozygous KI mice express hIL4 in serum after treatment with concanavalin.

Fig.2 Analysis of hIL4R expression in the spleen by FACS. The homozygous KI mice express hIL4R in the spleen, and the WT mice only express mIL4R.

Table 1. Blood routine test results of Hom hIL4/hIL4R mice (Data are presented as mean and ± SEM).

Table 2. Biochemistry examinations results of Hom hIL4/hIL4R mice (Data are presented as mean and ± SEM).

Fig.3 Evaluation of an Anti-huIL4Ra mAb in the OXA-Induced Atopic Dermatitis Model in hIL4/hIL4Ra dKI Mice.?(In cooperation with CrownBio)

Both dupilumab and Dexamethasone ameliorate overall atopic dermatitis activity in OXA - challenged ears, but only Dexamethasone worked in back skin.?

Fig.4 Dupilumab significantly mitigates inflammatory cell infiltration in lesioned ear. (In cooperation with CrownBio)?

Note: Inflammatory cell infiltration is indicated by black arrows, 10X images

Fig.5 Low dose dupilumab significantly mitigates inflammatory cell infiltration in lesioned skin.? (In cooperation with CrownBio)?

Note: Inflammatory cell infiltration is indicated by black arrows, 10X images

Fig.6 Dexamethasone and dupilumab treatments are well tolerated.?(In cooperation with CrownBio)?

Both significantly reduced IgE levels in serum but not spleen weight. Ordinary one-way ANOVA were applied for analysis compared to Isotype group, *P<0.05, **P<0.01, ***P<0.001.

Fig.7 Repeated OXA-induced Th2 cytokine production (hIL-4 elevation) and dupilumab treatment significantly reduces IL-6 and KC/GRO levels in lesioned ear. (In cooperation with CrownBio)?

Ordinary one-way ANOVA were applied for analysis compared to Isotype group, *P<0.05, **P<0.01, ***P<0.001.

Fig.8 Repeated OXA-induced Th2 cytokine production (hIL-4 elevation) and dupilumab treatment significantly reduces IL-5 and IL-2 levels in lesioned skin. (In cooperation with CrownBio)?

Ordinary one-way ANOVA were applied for analysis compared to Isotype group, *P<0.05, **P<0.01, ***P<0.001.

Case 1:?In vivo?efficacy of anti-human IL4RA mAb?in the?DNFB-induced Atopic dermatitis Model based on hIL4/hIL4R Mice

Fig.1 Body weight of DNFB-induced Atopic dermatitis Model?hIL4/hIL4R mice treated with dupilumab. (*P<0.05)?

Fig.2 Dupilumab ameliorate overall atopic dermatitis activity in DNFB-induced AD model. (*P<0.05, **P<0.01, ***P<0.001)

Fig.3 Dupilumab treatment significantly reduced IgE levels in serum and scratching times.?(A) day10 serum IgE (B) day16 serum IgE (C) scratch times on Day 12 (D) scratch times on Day 14. (*P<0.05, **P<0.01, ***P<0.001).

Fig.4? Dupilumab significantly mitigates inflammatory cell infiltration in lesioned skin on day 14. (A) dorsal image on day14; (B) Representative pathology images; (C) Inflammatory cell infiltration score; (D) neutrophils score; (E) eosinophils score; (F) epidermis thickness; (G) dermis thickness (*P<0.05, **P<0.01, ***P<0.001).

Case 2:?In vivo?efficacy of anti-human IL4RA mAb?in the OXA induced?Atopic dermatitis Model?based on hIL4/hIL4R Mice

Fig.1 OXA induced AD model in hIL4/hIL4R mice. (A) body weight (B) body weight change.?(n=6, Data are presented as Mean and ± SEM)

Fig.2 OXA induced AD model in hIL4/hIL4R mice. (A) gross observation on Day 21; (B) ear thickness (C) clinical score of skin.

Fig.3 OXA induced AD model in hIL4/hIL4R mice. (A) serum IgE (B) spleen weight.

Fig.4 OXA induced AD model in hIL4/hIL4R mice. (A) Pathology photos (B) Pathology score.

Case 3:?In vivo efficacy of anti-human IL4RA mAb?in the HDM induced Asthma Model?based on hIL4/hIL4R Mice

Fig.1 Body weight of HDM induced hIL4/hIL4R mice asthma model treated with dupilumab.? (n=6, Data are presented as Mean and ± SEM)

Fig.2 Dupilumab ameliorate overall asthma activity in HDM induced Asthma Model. (A) Inflammatory cell number in BALF. (B) Eosinophils cell number in Bronchoalveolar Lavage Fluid (BALF). (C) Eosinophils percentage in inflammatory cell. (D) Serum total IgE concentration.?(?**P<0.01, ***P<0.001)

Fig.3 HDM induced hIL4/hIL4R mice asthma model. (A) hIL-4 mRNA expression level. (B) mIL-8 mRNA expression level. (C) mIL-13 mRNA expression level. (D) mIL-6 mRNA expression level. (E) mIL-17a mRNA expression level. (*P<0.05, **P<0.01, ***P<0.001)

Fig.4 Dupilumab significantly mitigates the asthma symptoms in lung. (A) Representative images of H&E staining. (B) Pathology score results. Magnification, ×5.?(*P<0.05, **P<0.01, ***P<0.001)

Fig 5. HDM induced hIL4/hIL4R mice asthma model. (A) Representative images of PAS staining. (B) mucus score. Magnification, ×10.??(*P<0.05, ***P<0.001)