Tetraspanin CD53 Promotes Lymphocyte Recirculation by Stabilizing L-Selectin Surface Expression
Maria C. Demaria,
Louisa Yeung,
Rens Peeters,
Janet L. Wee,
Masa Mihaljcic,
Eleanor L. Jones,
Zeyad Nasa,
Frank Alderuccio,
Pamela Hall,
Brodie C. Smith,
Katrina J. Binger,
Gunther Hammerling,
Hang Fai Kwok,
Andrew Newman,
Ann Ager,
Annemiek van Spriel,
Michael J. Hickey,
Mark D. Wright
Affiliations
Maria C. Demaria
Department of Immunology and Pathology, Monash University, Alfred Research Alliance, Melbourne, VIC 3004, Australia
Louisa Yeung
Department of Immunology and Pathology, Monash University, Alfred Research Alliance, Melbourne, VIC 3004, Australia; Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre, 246 Clayton Road, Clayton, VIC 3168, Australia
Rens Peeters
Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
Janet L. Wee
Department of Immunology and Pathology, Monash University, Alfred Research Alliance, Melbourne, VIC 3004, Australia; Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre, 246 Clayton Road, Clayton, VIC 3168, Australia
Masa Mihaljcic
Department of Immunology and Pathology, Monash University, Alfred Research Alliance, Melbourne, VIC 3004, Australia
Eleanor L. Jones
Department of Immunology and Pathology, Monash University, Alfred Research Alliance, Melbourne, VIC 3004, Australia
Zeyad Nasa
Department of Immunology and Pathology, Monash University, Alfred Research Alliance, Melbourne, VIC 3004, Australia
Frank Alderuccio
Department of Immunology and Pathology, Monash University, Alfred Research Alliance, Melbourne, VIC 3004, Australia
Pamela Hall
Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre, 246 Clayton Road, Clayton, VIC 3168, Australia
Brodie C. Smith
Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre, 246 Clayton Road, Clayton, VIC 3168, Australia
Katrina J. Binger
Department of Biochemistry and Genetics, La Trobe Institute for Molecular Sciences, La Trobe University, Bundoora, VIC 3086, Australia
Gunther Hammerling
Molecular Immunology, German Cancer Research Center, Heidelberg, Germany
Hang Fai Kwok
Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, China
Andrew Newman
Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK
Ann Ager
Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK
Annemiek van Spriel
Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
Michael J. Hickey
Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre, 246 Clayton Road, Clayton, VIC 3168, Australia
Mark D. Wright
Department of Immunology and Pathology, Monash University, Alfred Research Alliance, Melbourne, VIC 3004, Australia; Corresponding author
Summary: Tetraspanins regulate key processes in immune cells; however, the function of the leukocyte-restricted tetraspanin CD53 is unknown. Here we show that CD53 is essential for lymphocyte recirculation. Lymph nodes of Cd53−/− mice were smaller than those of wild-type mice due to a marked reduction in B cells and a 50% decrease in T cells. This reduced cellularity reflected an inability of Cd53−/− B and T cells to efficiently home to lymph nodes, due to the near absence of L-selectin from Cd53−/− B cells and reduced stability of L-selectin on Cd53−/− T cells. Further analyses, including on human lymphocytes, showed that CD53 stabilizes L-selectin surface expression and may restrain L-selectin shedding via both ADAM17-dependent and ADAM17-independent mechanisms. The disruption in lymphocyte recirculation in Cd53−/− mice led to impaired immune responses dependent on antigen delivery to lymph nodes. Together these findings demonstrate an essential role for CD53 in lymphocyte trafficking and immunity.
