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

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

doi:10.1073/pnas.1503315112

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

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

Research output: Contribution to journal › Article › peer-review

144 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	11024-11029
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	112
Issue number	35
DOIs	https://doi.org/10.1073/pnas.1503315112
Publication status	Published - 18 Aug 2015
Externally published	Yes

Keywords

IL-22
tertiary lymphoid organs
chemokines
Sjogren's syndrome
autoimmunity

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Barone, F., Nayar, S., Campos, J., Cloake, T., Withers, D. R., Toellner, KM., Zhang, Y., Fouser, L., Fisher, B., Bowman, S., Rangel-Moreno, J., Garcia-Hernandez, M. L., Randall, T. D., Lucchesi, D., Bombardieri, M., Pitzalis, C., Luther, S. A., & Buckley, C. D. (2015). IL-22 regulates lymphoid chemokine production and assembly of tertiary lymphoid organs. Proceedings of the National Academy of Sciences of the United States of America, 112(35), 11024-11029. https://doi.org/10.1073/pnas.1503315112

IL-22 regulates lymphoid chemokine production and assembly of tertiary lymphoid organs. / Barone, F; Nayar, S; Campos, J; Cloake, T; Withers, D R; Toellner, KM; Zhang, Y; Fouser, L; Fisher, B; Bowman, S; Rangel-Moreno, J; Garcia-Hernandez, Mde L; Randall, T D; Lucchesi, D; Bombardieri, M; Pitzalis, C; Luther, S A; Buckley, C D.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 112, No. 35, 18.08.2015, p. 11024-11029.

Research output: Contribution to journal › Article › peer-review

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, ML, Randall, TD, Lucchesi, D, Bombardieri, M, Pitzalis, C, Luther, SA & Buckley, CD 2015, 'IL-22 regulates lymphoid chemokine production and assembly of tertiary lymphoid organs.', Proceedings of the National Academy of Sciences of the United States of America, vol. 112, no. 35, pp. 11024-11029. https://doi.org/10.1073/pnas.1503315112

Barone, F ; Nayar, S ; Campos, J ; Cloake, T ; Withers, D R ; Toellner, KM ; Zhang, Y ; Fouser, L ; Fisher, B ; Bowman, S ; Rangel-Moreno, J ; Garcia-Hernandez, Mde L ; Randall, T D ; Lucchesi, D ; Bombardieri, M ; Pitzalis, C ; Luther, S A ; Buckley, C D. / IL-22 regulates lymphoid chemokine production and assembly of tertiary lymphoid organs. In: Proceedings of the National Academy of Sciences of the United States of America. 2015 ; Vol. 112, No. 35. pp. 11024-11029.

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title = "IL-22 regulates lymphoid chemokine production and assembly of tertiary lymphoid organs.",

abstract = "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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AU - Nayar, S

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AU - Toellner, KM

AU - Zhang, Y

AU - Fouser, L

AU - Fisher, B

AU - Bowman, S

AU - Rangel-Moreno, J

AU - Garcia-Hernandez, Mde L

AU - Randall, T D

AU - Lucchesi, D

AU - Bombardieri, M

AU - Pitzalis, C

AU - Luther, S A

AU - Buckley, C D

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N2 - 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.

AB - 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.

KW - IL-22

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JF - Proceedings of the National Academy of Sciences of the United States of America

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ER -

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

Abstract

Keywords

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