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IL-10/Janus kinase/signal transducer and activator of transcription 3 signaling dysregulates Bim expression in autoimmune lymphoproliferative syndrome 

Published byLisa Astrid Bjørnstad Modified over 5 years ago

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Presentation on theme: "IL-10/Janus kinase/signal transducer and activator of transcription 3 signaling dysregulates Bim expression in autoimmune lymphoproliferative syndrome "— Presentation transcript:

1 IL-10/Janus kinase/signal transducer and activator of transcription 3 signaling dysregulates Bim expression in autoimmune lymphoproliferative syndrome  Omar Niss, MD, Allyson Sholl, MS, Jack J. Bleesing, MD, PhD, David A. Hildeman, PhD  Journal of Allergy and Clinical Immunology  Volume 135, Issue 3, Pages (March 2015) DOI: /j.jaci Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 Fig 1 Bim is increased in all T cell subsets of ALPS patients. The average fold increase in Bim mean fluorescence intensity (MFI ± SEM) in naive CD4+ (CD4n), memory CD4+ (CD4m), naive CD8+ (CD8n), memory CD8+ (CD8m) and double negative T cells: CD3+CD4−CD8−B220+(DNTB220+) from PBMCs. CD3+CD4−CD8−B220+ cells in ALPS patients were compared to CD3+CD4−CD8− cells in healthy controls, because the former are immeasurable in healthy controls. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 Fig 2 The expression of anti-apoptotic Bcl-2 molecules is heterogeneous in ALPS. The fold change in the MFI (±SEM) of different Bcl-2 family members in PBMCs of 12 ALPS patients versus healthy controls in naive (A) or memory (B) CD4 cells, naive (C) or memory (D) CD8 cells, and CD3+CD4−CD8−B220+ cells (E). The relative expression of Bim and different anti-apoptotic molecules (F) in DNTB220+ cells per patient (x axis). Dashed horizontal line represents the expression in healthy controls (ratio of 1). *Two data points are outside the axis limit. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4 Fig 3 Serum IL-10 level correlates with Bim before and after therapy. Results show the correlation of the increase in Bim expression in DNTC and serum IL-10 (A) or IL-6 (B) levels. Dashed lines represent the 95% CI. The change in serum IL-10 (C), the percentage of CD3+CD4−CD8− T cells (D), and Bim fold increase in DNTC (E) of 4 ALPS patients after therapy. Dashed horizontal line represents the expression in healthy controls. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5 Fig 4 Exogenous IL-10 partially upregulates Bim in normal T cells and ALPS DNTC in a Jak-dependent manner. Fold change in Bim expression in CD4+ (A), CD8+ (B), and DNTC (C) after culture with IL-10 ± ruxolitinib. pSTAT3 staining in T cells cultured in media or IL-10 ± ruxolitinib (D). IL-10 receptor MFI (±SEM) in CD3+CD4+, CD3+CD8+, and CD3+CD4−CD8−B220+ in ALPS patients and normal controls (E). Representative of 3 independent experiments with similar results. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

6 Fig 5 DNTC in ALPS are more sensitive to killing by ABT-737. A, The percentage of DNTC survival after culture with ABT-737 in ALPS patients and controls. B, The percentage of DNTC and CD4 T cell survival after culture with ABT-737 in ALPS patients. C, The percentage of DNTC and CD8 T cell survival after culture with ABT-737 in ALPS patients. Data are representative of 3 independent experiments in 6 ALPS patients. Points represent mean ± SEM. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

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