JAK inhibition prevents bleomycin-induced fibrosis in mice and is effective in morphea patients
Affiliations
- Department of Dermatology, Yale University, New Haven, CT, USA
Affiliations
- Department of Dermatology, UMass Medical School, Worcester, MA, USA
Affiliations
- Department of Dermatology, UMass Medical School, Worcester, MA, USA
Affiliations
- Department of Dermatology, UMass Medical School, Worcester, MA, USA
Affiliations
- Department of Dermatology, Yale University, New Haven, CT, USA
Affiliations
- Department of Pathology, UMass Medical School, Worcester, MA, USA
Affiliations
- Department of Pathology, UMass Medical School, Worcester, MA, USA
Affiliations
- Department of Dermatology, UMass Medical School, Worcester, MA, USA
Affiliations
- Department of Dermatology, UMass Medical School, Worcester, MA, USA
Affiliations
- Department of Dermatology, Yale University, New Haven, CT, USA
Correspondence
- Correspondence: Dr. Brett King, Department of Dermatology, Yale School of Medicine, 333 Cedar St, LCI 501, PO Box 208059, New Haven, CT 06510
Correspondence information about the author Brett KingAffiliations
- Department of Dermatology, Yale University, New Haven, CT, USA
Correspondence
- Correspondence: Dr. Brett King, Department of Dermatology, Yale School of Medicine, 333 Cedar St, LCI 501, PO Box 208059, New Haven, CT 06510
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Figure 1
JAK inhibition leads to improvement in patients with morphea and prevents bleomycin-induced fibrosis in mice. a, Patients treated with baricitinib (lower left) or tofacitinib. b, Gross, H&E, and trichrome (Tri) stained sections, scale bar: 50 μM. c, Morphea severity scores *Indicates that 2 patients had identical scores. d, Phospho-STAT1/3 staining in morphea, scale bar: 25 μM. e, Skin thickness (mean+/-SEM) in bleomycin-treated mice, V: vehicle, T: tofacitinib, R: ruxolitinib. f, Normal (Cont) and bleomycin-treated murine skin stained with phospho-STAT3, scale bar: 25 μM. g, Quantification of d. h, COL1A1 expression in human fibroblasts treated with bleomycin +/- JAK inhibitors (10 μM), normalized to HPRT1 expression. Dotted line: baseline COL1A1. ***p = 0.004 (vs Veh), **p = 0.038 (vs Veh). i, Quantification of f. j, Col1a1 expression (mean+/-SEM) in skin from bleomycin-treated mice; normalized to Actb. *p=0.07 vs Veh (V), **p=0.11 vs Veh, ***, p=0.04 vs Veh. All patients consented to publication of their clinical images.
Figure S1
Patient #2 had recurrence worsening of morphea and recurrence of ulcerative lesions after discontinuation of tofacitinb.
Figure S2
Sex-specific effects of bleomycin and JAKi treatment in mice. ++Two outlier values are outside the axis of the data displayed for male vehicle (87.2 and 51.7).
Abbreviations:
JAK (Janus kinase), STAT (signal transducer and activator of transcription), EF (eosinophilic fasciitis)To access this article, please choose from the options below
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