IL-22 regulates lymphoid chemokine production and assembly of tertiary lymphoid organs.

Barone F; Nayar S; Campos J; Cloake T; Withers DR; Toellner KM; Zhang Y; Fouser L; Fisher B; Bowman S; Rangel-Moreno J; Garcia-Hernandez Mde L; Randall TD; Lucchesi D; Bombardieri M; Pitzalis C; Luther SA; Buckley CD

doi:10.1073/pnas.1503315112

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Journal article

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

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Proceedings of the National Academy of Sciences of the United States of America. - 2015

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.

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