CD103+ pulmonary dendritic cells preferentially acquire and present apoptotic cell–associated antigen

Author:

Desch A. Nicole1,Randolph Gwendalyn J.22,Murphy Kenneth3,Gautier Emmanuel L.22,Kedl Ross M.1,Lahoud Mireille H.45,Caminschi Irina4,Shortman Ken45,Henson Peter M.111,Jakubzick Claudia V.11

Affiliation:

1. Department of Pediatrics, Department of Medicine, and Integrated Department of Immunology, National Jewish Health, University of Colorado Denver, Denver, CO 80206

2. Department of Development Regenerative Biology and Immunology Institute, Mount Sinai School of Medicine, New York, NY 10029

3. Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, MO 63130

4. The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia

5. Department of Medical Biology, The University of Melbourne, Melbourne, Victoria 3010, Australia

Abstract

Cells undergoing programmed cell death (apoptosis) are removed in situ by macrophages and dendritic cells (DCs) through a specialized form of phagocytosis (efferocytosis). In the lung, there are two primary DC subsets with the potential to migrate to the local lymph nodes (LNs) and initiate adaptive immune responses. In this study, we show that only CD103+ DCs were able to acquire and transport apoptotic cells to the draining LNs and cross present apoptotic cell–associated antigen to CD8 T cells. In contrast, both the CD11bhi and the CD103+ DCs were able to ingest and traffic latex beads or soluble antigen. CD103+ DCs selectively exhibited high expression of TLR3, and ligation of this receptor led to enhanced in vivo cytotoxic T cell responses to apoptotic cell–associated antigen. The selective role for CD103+ DCs was confirmed in Batf3−/− mice, which lack this DC subtype. Our findings suggest that CD103+ DCs are the DC subset in the lung that captures and presents apoptotic cell–associated antigen under homeostatic and inflammatory conditions and raise the possibility for more focused immunological targeting to CD8 T cell responses.

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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