IL-9 contributes to immunosuppression mediated by regulatory T cells and mast cells in B-cell non-hodgkin's lymphoma

J Clin Immunol. 2011 Dec;31(6):1084-94. doi: 10.1007/s10875-011-9584-9. Epub 2011 Sep 4.

Abstract

It has been known that regulatory T (Treg) cells and mast cells (MCs) are involved in tumor immunity regulation, but the exact roles and mechanisms of Treg cells and MCs in B-cell non-Hodgkin's lymphoma (NHL) are incompletely defined. In the present study, we found that the number of Foxp3(+) Treg cells and CD117(+) MCs increased in B-cell NHL patients. Concomitantly, a high level of interleukin (IL)-9 was observed in the sera from B-cell NHL patients. Neutralizing IL-9 significantly inhibited tumor growth in the lymphoma model of murine, and this process was associated with down-regulation of Treg cells and MCs. Furthermore, IL-9 was also demonstrated to induce expression of MC-related genes and proliferation of MCs from the bone marrow stem cells. Collectively, our results indicate that Treg cell and MCs are involved in immunosuppression in B-cell NHL, and IL-9 is a key mediator of Treg cells and MCs in that process. These findings provide novel insight for the pathogenesis and possible therapeutic strategy of B-cell NHL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Blocking / administration & dosage
  • B-Lymphocytes / pathology
  • Bone Marrow / pathology
  • Cells, Cultured
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Immunosuppression Therapy
  • Interleukin-9 / biosynthesis*
  • Interleukin-9 / blood
  • Interleukin-9 / genetics
  • Interleukin-9 / immunology
  • Lymphoma, Non-Hodgkin / blood
  • Lymphoma, Non-Hodgkin / drug therapy
  • Lymphoma, Non-Hodgkin / immunology*
  • Lymphoma, Non-Hodgkin / pathology
  • Mast Cells / drug effects
  • Mast Cells / immunology
  • Mast Cells / metabolism*
  • Mast Cells / pathology
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Transplantation
  • Proto-Oncogene Proteins c-kit / metabolism
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism*
  • T-Lymphocytes, Regulatory / pathology
  • Tumor Burden / drug effects

Substances

  • Antibodies, Blocking
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Interleukin-9
  • Proto-Oncogene Proteins c-kit