IL-22 regulates lymphoid chemokine production and assembly of tertiary lymphoid organs.
- Barone F Rheumatology Research Group, Centre for Translational Inflammation Research, School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, B15 2TT, United Kingdom; University of Birmingham Research Laboratories, Queen Elizabeth Hospital, Birmingham, B15 2WD, United Kingdom; f.barone@bham.ac.uk.
- Nayar S Rheumatology Research Group, Centre for Translational Inflammation Research, School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, B15 2TT, United Kingdom; University of Birmingham Research Laboratories, Queen Elizabeth Hospital, Birmingham, B15 2WD, United Kingdom;
- Campos J Rheumatology Research Group, Centre for Translational Inflammation Research, School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, B15 2TT, United Kingdom; University of Birmingham Research Laboratories, Queen Elizabeth Hospital, Birmingham, B15 2WD, United Kingdom;
- Cloake T Rheumatology Research Group, Centre for Translational Inflammation Research, School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, B15 2TT, United Kingdom; University of Birmingham Research Laboratories, Queen Elizabeth Hospital, Birmingham, B15 2WD, United Kingdom;
- Withers DR School of infection and Immunity, College of Medical and Dental Sciences, University of Birmingham, B15 2TT, United Kingdom;
- Toellner KM School of infection and Immunity, College of Medical and Dental Sciences, University of Birmingham, B15 2TT, United Kingdom;
- Zhang Y School of infection and Immunity, College of Medical and Dental Sciences, University of Birmingham, B15 2TT, United Kingdom;
- Fouser L Pfizer Research, Cambridge MA 02139-3526;
- Fisher B Rheumatology Research Group, Centre for Translational Inflammation Research, School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, B15 2TT, United Kingdom; University of Birmingham Research Laboratories, Queen Elizabeth Hospital, Birmingham, B15 2WD, United Kingdom;
- Bowman S Rheumatology Research Group, Centre for Translational Inflammation Research, School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, B15 2TT, United Kingdom; University of Birmingham Research Laboratories, Queen Elizabeth Hospital, Birmingham, B15 2WD, United Kingdom;
- Rangel-Moreno J Division of Allergy, Immunology and Rheumatology, Department of Medicine, University of Rochester, Rochester, NY 14642;
- Garcia-Hernandez Mde L Division of Allergy, Immunology and Rheumatology, Department of Medicine, University of Rochester, Rochester, NY 14642;
- Randall TD Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294-2182;
- Lucchesi D Centre for Experimental Medicine and Rheumatology, Queen Mary University of London, EC1M 6BQ, London United Kingdom;
- Bombardieri M Centre for Experimental Medicine and Rheumatology, Queen Mary University of London, EC1M 6BQ, London United Kingdom;
- Pitzalis C Centre for Experimental Medicine and Rheumatology, Queen Mary University of London, EC1M 6BQ, London United Kingdom;
- Luther SA Department of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland.
- Buckley CD Rheumatology Research Group, Centre for Translational Inflammation Research, School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, B15 2TT, United Kingdom; University of Birmingham Research Laboratories, Queen Elizabeth Hospital, Birmingham, B15 2WD, United Kingdom;
- 2015-08-20
Published in:
- Proceedings of the National Academy of Sciences of the United States of America. - 2015
IL-22
Sjogren's syndrome
autoimmunity
chemokines
tertiary lymphoid organs
Animals
Autoantibodies
B-Lymphocytes
Chemokines, CXC
Interleukins
Lymphoid Tissue
Mice
Mice, Knockout
English
The series of events leading to tertiary lymphoid organ (TLO) formation in mucosal organs following tissue damage remain unclear. Using a virus-induced model of autoantibody formation in the salivary glands of adult mice, we demonstrate that IL-22 provides a mechanistic link between mucosal infection, B-cell recruitment, and humoral autoimmunity. IL-22 receptor engagement is necessary and sufficient to promote differential expression of chemokine (C-X-C motif) ligand 12 and chemokine (C-X-C motif) ligand 13 in epithelial and fibroblastic stromal cells that, in turn, is pivotal for B-cell recruitment and organization of the TLOs. Accordingly, genetic and therapeutic blockade of IL-22 impairs and reverses TLO formation and autoantibody production. Our work highlights a critical role for IL-22 in TLO-induced pathology and provides a rationale for the use of IL-22-blocking agents in B-cell-mediated autoimmune conditions.
- Language
-
- English
- Open access status
- bronze
- Identifiers
-
- DOI 10.1073/pnas.1503315112
- PMID 26286991
- Persistent URL
- https://sonar.ch/global/documents/238958
Statistics
Document views: 82
File downloads:
- Full-text: 0