Loss of SOCS7 in mice results in severe cutaneous disease and increased mast cell activation

• Published in: Clinical immunology (Orlando, Fla.) Vol. 132; no. 2; pp. 277 - 284
• Main Authors: Knisz, Judit, Banks, Alex, McKeag, Lisa, Metcalfe, Dean D, Rothman, Paul B, Brown, Jared M
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.08.2009; Elsevier
• Subjects: Allergic diseases; Allergy; Allergy and Immunology; Animals; Atopic dermatitis; Biological and medical sciences; Blotting, Western; Bone Marrow Cells - cytology; Bone Marrow Cells - metabolism; Cells, Cultured; Cytokines - genetics; Cytokines - metabolism; Enzyme-Linked Immunosorbent Assay; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Immunoglobulin E - blood; Immunoglobulin G - blood; Immunopathology; Interleukin-13 - biosynthesis; Interleukin-6 - biosynthesis; Mast cell; Mast Cells - cytology; Mast Cells - metabolism; Medical sciences; Mice; Mice, Inbred Strains; Mice, Knockout; Receptors, IgE - metabolism; Receptors, Interleukin-7 - genetics; Receptors, Interleukin-7 - metabolism; Reverse Transcriptase Polymerase Chain Reaction; Skin allergic diseases. Stinging insect allergies; Skin Diseases - blood; Skin Diseases - genetics; Skin Diseases - physiopathology; SOCS; Suppressor of cytokine signaling; Suppressor of Cytokine Signaling Proteins - deficiency; Suppressor of Cytokine Signaling Proteins - genetics; Suppressor of Cytokine Signaling Proteins - physiology; TSLP; Tumor Necrosis Factor-alpha - biosynthesis; 2,4-Dinitrophenol-Human Serum Albumin; Allergy; Bone Marrow Derived Mast Cells; AD; Atopic Dermatitis; TSLP; TSLPR; SOCS; Immunoglobulin; Suppressor of Cytokine Signaling; DNP-HSA; Thymic Stromal Lymphopoietin; Mast cell; BMMC; Ig; TSLP Receptor; Atopic dermatitis; Suppressor of cytokine signaling; Immunopathology; Skin disease; signaling; Rodentia; Cytokine; Activation; Atopy; Suppressor of cytokine; Signal transduction; Vertebrata; Mammalia; Immunology; Thymic stromal lymphopoietin; Mouse; Animal; Suppressor; Suppressor of cytokine signalling
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2009.04.003

Abstract The Suppressor of Cytokine Signaling (SOCS) protein family plays a central role in the negative regulation of cytokine action and has been implicated in the development of atopic diseases. Lack of SOCS7 is associated with severe skin disease in mice. We sought to explore the underlying mechanisms resulting in this phenotype. Skin samples were analyzed and serum immunoglobulin production was measured. Cytokine production by bone marrow derived mast cells was determined by ELISA. Mast cell thymic stromal lymphopoietin (TSLP) production was assessed by quantitative real-time PCR. Data obtained revealed that Socs7−/− mice have increased serum IgE and IgG1 production and exhibit an increased mast cell infiltrate, as well as un-provoked mast cell degranulation in the dermis as compared to controls. In vitro , bone marrow derived mast cells from Socs7−/− mice are hyperactive to IgE-mediated stimuli, with elevated production of pro-inflammatory cytokines (IL-13, IL-6, TNF-α). Further, activated Socs7−/− bone marrow derived mast cells have increased IL-7Rα transcript, which is part of the heterodimeric receptor for TSLP. Finally, lack of SOCS7 was accompanied by an increase in TSLP mRNA and protein production by mast cells following FcεRI aggregation. These data implicate SOCS7 in the modulation of allergic inflammation and demonstrate that SOCS7 is involved in the regulation of TSLP signaling in mast cells.