Elevated IL-17 produced by TH17 cells promotes myeloma cell growth and inhibits immune function in multiple myeloma

被引：289

作者：

Prabhala, Rao H. ^{[1
,2
,3
]}

Pelluru, Dheeraj ^{[1
]}

Fulciniti, Mariateresa ^{[1
]}

Prabhala, Harsha K. ^{[4
]}

Nanjappa, Puru ^{[1
]}

Song, Weihua ^{[1
]}

Pai, Christine ^{[2
]}

Amin, Samir ^{[1
]}

Tai, Yu-Tzu ^{[1
]}

Richardson, Paul G. ^{[1
]}

Ghobrial, Irene M. ^{[1
]}

Treon, Steven P. ^{[1
]}

Daley, John F. ^{[1
]}

Anderson, Kenneth C. ^{[1
,3
]}

Kutok, Jeffery L. ^{[3
]}

Munshi, Nikhil C. ^{[1
,2
,3
]}

机构：

[1] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA

[2] Vet Adm Boston Healthcare Syst, W Roxbury, MA USA

[3] Brigham & Womens Hosp, Boston, MA 02115 USA

[4] Univ Virginia, Sch Med, MD PhD Program, Charlottesville, VA 22908 USA

来源：

BLOOD | 2010年 / 115卷 / 26期

基金：

美国国家卫生研究院;

关键词：

T-HELPER-CELLS; ROR-GAMMA-T; DENDRITIC CELLS; INNATE IMMUNITY; HOST-DEFENSE; BONE-MARROW; FACTOR-BETA; TH17; CELLS; INTERLEUKIN-17; RECEPTOR;

D O I：

10.1182/blood-2009-10-246660

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Elevated cytokines in bone marrow (BM) micro-environment (interleukin-6 [IL-6], transforming growth factor-beta [TGF-beta], and IL-1 beta) may play an important role in observed immune dysfunction in multiple myeloma (MM). As IL-6 and TGF-beta are important for the generation of T-helper 17 (T(H)17) cells, we evaluated and observed a significantly elevated baseline and induced frequency of T(H)17 cells in peripheral blood mononuclear cells (PBMCs) and BM mononuclear cells (BMMCs) from MM patients compared with healthy donors. We observed significant increase in levels of serum IL-17, IL-21, IL-22, and IL-23 in blood and BM in MM compared with healthy donors. We also observed that myeloma PBMCs after T(H)17 polarization significantly induced IL-1 alpha, IL-13, IL-17, and IL-23 production compared with healthy donor PBMCs. We next observed that IL-17 promotes myeloma cell growth and colony formation via IL-17 receptor, adhesion to bone marrow stromal cells (BMSCs) as well as increased growth in vivo in murine xenograft model of human MM. Additionally, we have observed that combination of IL-17 and IL-22 significantly inhibited the production of T(H)1-mediated cytokines, including interferon-gamma (IFN-gamma), by healthy donor PBMCs. In conclusion, IL-17-producing T(H)17 cells play an important role in MM pathobiology and may be an important therapeutic target for anti-MM activity and to improve immune function. (Blood. 2010; 115(26): 5385-5392)

引用

页码：5385 / 5392

页数：8

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