Autoimmune manifestations in aged mice arise from early-life immune dysregulation

Tamer I. Mahmoud; Jingya Wang; Jodi L. Karnell; Qiming Wang; Shu Wang; Brian Naiman; Phillip Gross; Philip Z. Brohawn; Chris Morehouse; Jordan Aoyama; Clive Wasserfall; Laura Carter; Mark A. Atkinson; David V. Serreze; Helen Braley-Mullen; Tomas Mustelin; Roland Kolbeck; Ronald Herbst; Rachel Ettinger

doi:10.1126/scitranslmed.aag0367

Research ArticleAutoimmunity

Autoimmune manifestations in aged mice arise from early-life immune dysregulation

Tamer I. Mahmoud¹,*,
Jingya Wang¹,†,
Jodi L. Karnell¹,†,
Qiming Wang²,‡,
Shu Wang¹,
Brian Naiman¹,
Phillip Gross¹,
Philip Z. Brohawn³,
Chris Morehouse³,
Jordan Aoyama³,
Clive Wasserfall⁴,
Laura Carter¹,§,
Mark A. Atkinson⁴,
David V. Serreze²,
Helen Braley-Mullen⁵,
Tomas Mustelin¹,
Roland Kolbeck¹,
Ronald Herbst¹ and
Rachel Ettinger¹,¶

¹Respiratory, Inflammation, and Autoimmunity Group, MedImmune LLC, Gaithersburg, MD 20878, USA.
²The Jackson Laboratory, Bar Harbor, ME 04609, USA.
³Translational Sciences–Pharmacogenomics, MedImmune LLC, Gaithersburg, MD 20878, USA.
⁴Departments of Pathology and Pediatrics, University of Florida, Gainesville, FL 32610, USA.
⁵Department of Medicine, University of Missouri, Columbia, MO 65212, USA.

↵¶Corresponding author. Email: ettingerc{at}medimmune.com

↵* Present address: Bristol-Myers Squibb, Princeton, NJ 08540, USA.
↵† These authors contributed equally to this work.
↵‡ Present address: Graduate Program in Genetics, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA 02111, USA.
↵§ Present address: Lycera Corp., Ann Arbor, MI 48109, USA.

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Science Translational Medicine 19 Oct 2016:
Vol. 8, Issue 361, pp. 361ra137
DOI: 10.1126/scitranslmed.aag0367

Tamer I. Mahmoud

1Respiratory, Inflammation, and Autoimmunity Group, MedImmune LLC, Gaithersburg, MD 20878, USA.

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Jingya Wang

1Respiratory, Inflammation, and Autoimmunity Group, MedImmune LLC, Gaithersburg, MD 20878, USA.

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Jodi L. Karnell

1Respiratory, Inflammation, and Autoimmunity Group, MedImmune LLC, Gaithersburg, MD 20878, USA.

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Qiming Wang

2The Jackson Laboratory, Bar Harbor, ME 04609, USA.

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Shu Wang

1Respiratory, Inflammation, and Autoimmunity Group, MedImmune LLC, Gaithersburg, MD 20878, USA.

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Brian Naiman

1Respiratory, Inflammation, and Autoimmunity Group, MedImmune LLC, Gaithersburg, MD 20878, USA.

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Phillip Gross

1Respiratory, Inflammation, and Autoimmunity Group, MedImmune LLC, Gaithersburg, MD 20878, USA.

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Philip Z. Brohawn

3Translational Sciences–Pharmacogenomics, MedImmune LLC, Gaithersburg, MD 20878, USA.

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Chris Morehouse

3Translational Sciences–Pharmacogenomics, MedImmune LLC, Gaithersburg, MD 20878, USA.

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Jordan Aoyama

3Translational Sciences–Pharmacogenomics, MedImmune LLC, Gaithersburg, MD 20878, USA.

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Clive Wasserfall

4Departments of Pathology and Pediatrics, University of Florida, Gainesville, FL 32610, USA.

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Laura Carter

1Respiratory, Inflammation, and Autoimmunity Group, MedImmune LLC, Gaithersburg, MD 20878, USA.

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Mark A. Atkinson

4Departments of Pathology and Pediatrics, University of Florida, Gainesville, FL 32610, USA.

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David V. Serreze

2The Jackson Laboratory, Bar Harbor, ME 04609, USA.

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Helen Braley-Mullen

5Department of Medicine, University of Missouri, Columbia, MO 65212, USA.

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Tomas Mustelin

1Respiratory, Inflammation, and Autoimmunity Group, MedImmune LLC, Gaithersburg, MD 20878, USA.

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Roland Kolbeck

1Respiratory, Inflammation, and Autoimmunity Group, MedImmune LLC, Gaithersburg, MD 20878, USA.

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Ronald Herbst

1Respiratory, Inflammation, and Autoimmunity Group, MedImmune LLC, Gaithersburg, MD 20878, USA.

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Rachel Ettinger

1Respiratory, Inflammation, and Autoimmunity Group, MedImmune LLC, Gaithersburg, MD 20878, USA.

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For correspondence: ettingerc@medimmune.com

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Autoimmune manifestations are driven by peripheral immune dysregulation in early life and are prevented by prophylactic targeting of the CD40/CD40L pathway.

Autoimmune manifestations in aged mice arise from early-life immune dysregulation

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