A novel role of IL-17-producing lymphocytes in mediating lytic bone disease in multiple myeloma

Kimberly Noonan, Luigi Marchionni, Judy Anderson, Drew Pardoll, G. David Roodman, Ivan Borrello

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

Osteoclast (OC)-mediated lytic bone disease remains a cause of major morbidity in multiple myeloma. Here we demonstrate the critical role of interleukin-17-producing marrow infiltrating lymphocytes (MILs) in OC activation and development of bone lesions in myeloma patients. Unlike MILs from normal bone marrow, myeloma MILs possess few regulatory T cells (Tregs) and demonstrate an interleukin-17 phenotype that enhances OC activation. In univariate analyses of factors mediating bone destruction, levels of cytokines that selectively induce and maintain the Th17 phenotype tightly correlated with the extent of bone disease in myeloma. In contrast, MILs activated under conditions that skew toward a Th1 phenotype significantly reduced formation of mature OC. These findings demonstrate that interleukin-17 T cells are critical to the genesis of myeloma bone disease and that immunologic manipulations shifting MILs from a Th17 to a Th1 phenotype may profoundly diminish lytic bone lesions in multiple myeloma.

Original languageEnglish (US)
Pages (from-to)3554-3563
Number of pages10
JournalBlood
Volume116
Issue number18
DOIs
StatePublished - Nov 4 2010
Externally publishedYes

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Lymphocytes
Interleukin-17
Bone Diseases
Multiple Myeloma
Bone
Bone Marrow
Osteoclasts
Phenotype
T-cells
Bone and Bones
Chemical activation
Bone Development
Regulatory T-Lymphocytes
Statistical Factor Analysis
Cytokines
Morbidity
T-Lymphocytes

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

A novel role of IL-17-producing lymphocytes in mediating lytic bone disease in multiple myeloma. / Noonan, Kimberly; Marchionni, Luigi; Anderson, Judy; Pardoll, Drew; Roodman, G. David; Borrello, Ivan.

In: Blood, Vol. 116, No. 18, 04.11.2010, p. 3554-3563.

Research output: Contribution to journalArticle

Noonan, K, Marchionni, L, Anderson, J, Pardoll, D, Roodman, GD & Borrello, I 2010, 'A novel role of IL-17-producing lymphocytes in mediating lytic bone disease in multiple myeloma', Blood, vol. 116, no. 18, pp. 3554-3563. https://doi.org/10.1182/blood-2010-05-283895
Noonan, Kimberly ; Marchionni, Luigi ; Anderson, Judy ; Pardoll, Drew ; Roodman, G. David ; Borrello, Ivan. / A novel role of IL-17-producing lymphocytes in mediating lytic bone disease in multiple myeloma. In: Blood. 2010 ; Vol. 116, No. 18. pp. 3554-3563.
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