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Science 323 (5922): 1722-1725

Copyright © 2009 by the American Association for the Advancement of Science

CD24 and Siglec-10 Selectively Repress Tissue Damage–Induced Immune Responses

Guo-Yun Chen,1 Jie Tang,4 Pan Zheng,1,2* Yang Liu1,3*

Abstract: Patten recognition receptors, which recognize pathogens or components of injured cells (danger), trigger activation of the innate immune system. Whether and how the host distinguishes between danger- versus pathogen-associated molecular patterns remains unresolved. We report that CD24-deficient mice exhibit increased susceptibility to danger- but not pathogen-associated molecular patterns. CD24 associates with high mobility group box 1, heat shock protein 70, and heat shock protein 90; negatively regulates their stimulatory activity; and inhibits nuclear factor {kappa}B (NF-{kappa}B) activation. This occurs at least in part through CD24 association with Siglec-10 in humans or Siglec-G in mice. Our results reveal that the CD24–Siglec G pathway protects the host against a lethal response to pathological cell death and discriminates danger- versus pathogen-associated molecular patterns.

1 Division of Immunotherapy, Department of Surgery, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.
2 Department of Pathology, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.
3 Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.
4 Institute of Biophysics, Chinese Academy of Science, Beijing, China.

* To whom correspondence should be addressed. E-mail: yangl{at} (Y.L.), panz{at} (P.Z.)

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