Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 112, Issue 35, Pages 11024-11029Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1503315112
Keywords
IL-22; tertiary lymphoid organs; chemokines; Sjogren's syndrome; autoimmunity
Categories
Funding
- Wellcome Trust
- Arthritis Research UK [19791]
- BBSRC [BB/M025292/1] Funding Source: UKRI
- MRC [G1001390, MR/N003063/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/M025292/1] Funding Source: researchfish
- Medical Research Council [MR/N003063/1, G1001390] Funding Source: researchfish
- Versus Arthritis [19791] Funding Source: researchfish
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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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