Anti-HMGB1 Monoclonal Antibody Ameliorates Immunosuppression after Peripheral Tissue Trauma: Attenuated T-Lymphocyte Response and Increased Splenic CD11b+Gr-1+Myeloid-Derived Suppressor Cells Require HMGB1

Author:

Ruan Xiangcai12,Darwiche Sophie S.2,Cai Changchun2,Scott Melanie J.2,Pape Hans-Christoph3,Billiar Timothy R.2

Affiliation:

1. Department of Anesthesiology, First Municipal People’s Hospital of Guangzhou, Affiliated Hospital of Guangzhou Medical College, Guangzhou, China

2. Department of Surgery, University of Pittsburgh, University of Pittsburgh Medical Center, Suite F1281, 200 Lothrop Street, Pittsburgh, PA 15213, USA

3. Department of Orthopaedic and Trauma Surgery, Aachen University Hospital, Pauwelsstraße 30, 52074 Aachen, Germany

Abstract

Although tissue-derived high mobility group box 1 (HMGB1) is involved in many aspects of inflammation and tissue injury after trauma, its role in trauma-induced immune suppression remains elusive. Using an established mouse model of peripheral tissue trauma, which includes soft tissue and fracture components, we report here that treatment with anti-HMGB1 monoclonal antibody ameliorated the trauma-induced attenuated T-cell responses and accumulation of CD11b+Gr-1+myeloid-derived suppressor cells in the spleens seen two days after injury. Our data suggest that HMGB1 released after tissue trauma contributes to signaling pathways that lead to attenuation of T-lymphocyte responses and enhancement of myeloid-derived suppressor cell expansion.

Funder

National Institutes of Health

Publisher

Hindawi Limited

Subject

Cell Biology,Immunology

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