Elevated IL-17 produced by Th17 cells promotes myeloma cell growth and inhibits immune function in multiple myeloma

Prabhala, Rao; Pelluru, Dheeraj; Fulciniti, Mariateresa; Prabhala, Harsha; Nanjappa, Puru; Wu, Song; Pai, Christine; Amin, Samir B.; Tai, Yu‐Tzu; Richardson, Paul G.; Ghobrial, Irène M.; Treon, Steven P.; Daley, John; Anderson, Kenneth C.; Kutok, Jeffery L.; Munshi, Nikhil C.

doi:10.1182/blood-2009-10-246660

Cited by 297 publications

(293 citation statements)

References 49 publications

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“…2A). These data are in agreement with Bryant C et al, 28 who also did not find a significant increase of Th17 cells in the blood of MM patients compared with normal controls and in partial agreement with the results from Prabhala RH et al, 15 who found a significantly elevated frequency of Th17 cells in PB but not in BM of MM patients compared with healthy controls.…”

Section: Th17 and Th22 Cells Within The Same Cohort Of MM Patientssupporting

confidence: 82%

“…In addition to the correlation with the extent of bone disease, 17 it has been recently reported that primary immature dendritic cells in MM are prone to osteoclast-like trans-differentiation after IL-17 stimulation. 24 Other roles have been ascribed to IL-17, such as promotion of MM cell growth/survival, which is supported by the expression of the IL-17 receptor on MM cell lines and primary tumors, 15,25 and inhibition of immune cell functions. 15 However, no direct correlation between Th17 cell numbers and disease prognosis and/or severity has been provided.…”

Section: Th17 Cells In MMmentioning

confidence: 99%

“…24 Other roles have been ascribed to IL-17, such as promotion of MM cell growth/survival, which is supported by the expression of the IL-17 receptor on MM cell lines and primary tumors, 15,25 and inhibition of immune cell functions. 15 However, no direct correlation between Th17 cell numbers and disease prognosis and/or severity has been provided. T regulatory cells (Tregs) are often studied in relation to Th17 cells, as their differentiation is mutually controlled, and the Treg/Th17 balance is considered to be a marker of immunoregulatory function.…”

Section: Th17 Cells In MMmentioning

confidence: 99%

“…The profile of cytokines released (i.e., IL-17 alone or in association with IFN-g in the case of poly-functional Th17-Th1 cells) has been linked to one or more aspects of MM pathology, such as increase in osteoclastogenesis, promotion of MM cell growth and inhibition of immune function. [15][16][17] A proosteoclastogenic activity of Th17 cells had been first described in the context of autoimmune arthritis, 18 where arthritogenic Th17 cells are recruited to the inflamed tissues through a CCL20-CCR6 axis. 19 A similar mechanism of bone erosion has been hypothesized in MM, where IL-17 mediates up-regulation by BM cells of the expression of the receptor activator of NF-kB ligand (RANKL), which is a differentiation factor for osteoclasts and whose natural soluble antagonist is osteoprotegerin (OPG).…”

Section: Th17 Cells In MMmentioning

confidence: 99%

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Non-redundant roles for Th17 and Th22 cells in multiple myeloma clinical correlates

2015

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Section: Th17 and Th22 Cells Within The Same Cohort Of MM Patientssupporting

confidence: 82%

Section: Th17 Cells In MMmentioning

confidence: 99%

Section: Th17 Cells In MMmentioning

confidence: 99%

Section: Th17 Cells In MMmentioning

confidence: 99%

See 2 more Smart Citations

Non-redundant roles for Th17 and Th22 cells in multiple myeloma clinical correlates

2015

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“…Recently, Prabhala et al reported that Th17 cells appear to be involved in the pathogenesis of multiple myeloma [18]. They determined that elevated levels of IL-17, produced by Th17 cells, promote the growth of myeloma cells.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of RORγt under control of the CD2 promoter induces polyclonal plasmacytosis and autoantibody production in transgenic mice

et al. 2012

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Retinoic acid related orphan receptor gamma-t (RORγt) is known to be a master regulator of Th17-cell development. In this study, we generated RORγt-overexpressing transgenic (RORγt Tg) mice in which transgene expression was driven by the CD2 promoter, and found that these mice developed polyclonal plasmacytosis and autoantibody production. RORγt Tg mice were generated on a C57BL/6 background, and also were intercrossed with BALB/c mice. BALB/c F1 (BALB/F1) RORγt Tg mice developed massive polyclonal plasmacytosis, and had shorter life spans. Splenomegaly and infiltration of plasma cells into the lung were observed. Hyperglobulinemia, anti-double-stranded DNA antibodies, antierythrocyte antibodies, and anti-platelet antibodies were detected in BALB/F1 RORγt Tg mice. In the present study, polyclonal plasmacytosis in BALB/F1 RORγt Tg mice appeared to be due to the induction of excessive IL-6 production by IL-17. We detected increased numbers of CD11b + cells that produced IL-6. We also generated IL-6-deficient RORγt Tg BALB/F1 background mice, which displayed high levels of serum IL-17, but did not develop severe hyperglobulinemia. Excessive IL-6 production by several cell types, including macrophages, in BALB/F1 RORγt Tg mice, might effect the development of plasmacytosis. These results suggest that RORγt plays important roles in the development of plasmacytosis and autoantibody production. Eur. J. Immunol. 2012Immunol. . 42: 1999Immunol. -2009 Introduction CD4 + T helper (Th) cells are a subcategory of T lymphocytes that play a central role in modulating immune responses. Classically, naïve CD4 + T cells have been thought to differentiate into two cell types, Th1 and Th2 cells. This corresponds to the Th1/Th2 paradigm proposed by Mosmann et al. [1]. More recently, a third subset of Th cells, Th17 cells, has been described; this is a distinct lineage that does not share developmental pathways with either Th1 or Th2 cells [2,3]. Th17 cells are generally thought to be proinflammatory, especially through the production of 3]. Th17 cells have been shown to participate in the development of autoimmunity, and also to play an important role in host defense against infection [4]. Expression of the transcription factor retinoic acid related orphan receptor gamma-t (RORγt) is required for the differentiation of Th17 cells [5,6]. The orphan receptor RORγt is a thymusspecific isoform of RORγ [7]. A related nuclear receptor, RORα, was shown to act in synergy with RORγt to promote the differentiation of Th17 cells [8]. STAT3 is also required for full generation of the Th17 lineage [9]. The upregulation of RORγt depends on STAT3 [9], and the selective deletion of STAT3 in T cells partially abrogates the development of Th17 cells because it also abrogates the expression of RORα and RORγt [8].IL-6 is an important cytokine in the differentiation of Th17 cells. IL-6, together with TGF-β, is required to induce IL-17 expression in naïve CD4 + T cells, which are characterized by the expression of RORγt [5,10,11]. Since its discovery i...

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Silicon‐Based Biomaterials Modulate the Adaptive Immune Response of T Lymphocytes to Promote Osteogenesis/Angiogenesis via Epigenetic Regulation

Xia,

Wu,

Chen

et al. 2023

Adv Healthcare Materials

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Silicon (Si)‐based biomaterials have been widely applied for bone regeneration. However, the underlying mechanisms of the materials function remain largely unknown. T lymphocyte‐mediated adaptive immune response plays a vital role in the process of bone regeneration. In the current study, mesoporous silica (MS) was used as a model material of Si‐based biomaterials. It showed that the supernatant of CD4+ T lymphocytes pretreated with MS extract significantly promoted the vascularized bone regeneration. The potential mechanism is closely related to the fact that MS extract could reduce the expression of regulatory factor X‐1 (RFX‐1) in CD4+ T lymphocytes. This might result in the overexpression of interleukin‐17A (IL‐17A) by boosting histone H3 acetylation and lowering DNA methylation and H3K9 trimethylation. Importantly, the in vivo experiments further revealed that MS particles significantly enhanced bone regeneration with improved angiogenesis in the critical‐sized calvarial defect mouse model accompanied by upregulation of IL‐17A in peripheral blood and the proportion of Th17 cells. Our study suggests that modulation of the adaptive immune response of T lymphocytes by Silicate‐based biomaterials plays an important role for bone regeneration.This article is protected by copyright. All rights reserved

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Elevated IL-17 produced by Th17 cells promotes myeloma cell growth and inhibits immune function in multiple myeloma

Cited by 297 publications

References 49 publications

Non-redundant roles for Th17 and Th22 cells in multiple myeloma clinical correlates

Non-redundant roles for Th17 and Th22 cells in multiple myeloma clinical correlates

Overexpression of RORγt under control of the CD2 promoter induces polyclonal plasmacytosis and autoantibody production in transgenic mice

Silicon‐Based Biomaterials Modulate the Adaptive Immune Response of T Lymphocytes to Promote Osteogenesis/Angiogenesis via Epigenetic Regulation

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