A novel role for IL-22R1 as a driver of inflammation

Ram Savan, Adelle P. McFarland, Della A. Reynolds, Lionel Feigenbaum, Karthika Ramakrishnan, Megan Karwan, Hidekazu Shirota, Dennis M. Klinman, Kieron Dunleavy, Stefania Pittaluga, Stephen K. Anderson, Raymond P. Donnelly, Wyndham H. Wilson, Howard A. Young

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

The interleukin (IL)-22R1 chain of the heterodimeric IL-22 receptor is not expressed on normal leukocytes, but this receptor is expressed on T cells from anaplastic lymphoma kinase-positive (ALK+) anaplastic large cell lymphoma (ALCL) patients. To investigate the consequences of aberrant expression of this receptor on lymphocytes, we generated transgenic mice that express IL-22R1 on lymphocytes. The health of these animals progressively deteriorated at 8 to 12 weeks of age, as they displayed respiratory distress, rough coat and sluggish movement, and subsequent lethality due to multiorgan inflammation. The IL-22R1 transgenic animals developed neutrophilia that correlated with increased levels of circulating IL-17 and granulocyte colony-stimulating factor. In addition, these mice had increased serum IL-22 levels, suggesting that T cells expressing IL-22R1 generate IL-22 in a positive autoregulatory loop. As a result of the mouse model findings, we analyzed circulating cytokine levels in ALK+ALCL patients and detected elevated levels of IL-22, IL-17, and IL-8 in untreated patient samples. Importantly, IL-22 and IL-17 were undetectable in all patients who were in complete remission after chemotherapy. This study documents a previously unknown role of IL-22R1 in inflammation and identifies the involvement of IL-22R1/IL-22 in ALK+ALCL.

Original languageEnglish
Pages (from-to)575-584
Number of pages10
JournalBlood
Volume117
Issue number2
DOIs
Publication statusPublished - 2011 Jan 13
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Savan, R., McFarland, A. P., Reynolds, D. A., Feigenbaum, L., Ramakrishnan, K., Karwan, M., Shirota, H., Klinman, D. M., Dunleavy, K., Pittaluga, S., Anderson, S. K., Donnelly, R. P., Wilson, W. H., & Young, H. A. (2011). A novel role for IL-22R1 as a driver of inflammation. Blood, 117(2), 575-584. https://doi.org/10.1182/blood-2010-05-285908