Title
IL-21-Driven Neoplasms in SJL Mice Mimic Some Key Features of Human Angioimmunoblastic T-Cell Lymphoma.
Document Type
Article
Publication Date
11-2015
JAX Source
Am J Pathol 2015 Nov; 185(11):3102-14.
Volume
185
Issue
11
First Page
3102
Last Page
3114
ISSN
1525-2191
PMID
26363366
Abstract
SJL/J mice exhibit a high incidence of mature B-cell lymphomas that require CD4(+) T cells for their development. We found that their spleens and lymph nodes contained increased numbers of germinal centers and T follicular helper (TFH) cells. Microarray analyses revealed high levels of transcripts encoding IL-21 associated with high levels of serum IL-21. We developed IL-21 receptor (IL21R)-deficient Swiss Jim Lambart (SJL) mice to determine the role of IL-21 in disease. These mice had reduced numbers of TFH cells, lower serum levels of IL-21, and few germinal center B cells, and they did not develop B-cell tumors, suggesting IL-21-dependent B-cell lymphomagenesis. We also noted a series of features common to SJL disease and human angioimmunoblastic T-cell lymphoma (AITL), a malignancy of TFH cells. Gene expression analyses of AITL showed that essentially all cases expressed elevated levels of transcripts for IL21, IL21R, and a series of genes associated with TFH cell development and function. These results identify a mouse model with features of AITL and suggest that patients with the disease might benefit from therapeutic interventions that interrupt IL-21 signaling. Am J Pathol 2015 Nov; 185(11):3102-14.
Recommended Citation
Jain S,
Chen J,
Nicolae A,
Wang H,
Shin D,
Adkins EB,
Sproule TJ,
Leeth C,
Sakai T,
Kovalchuk A,
Raffeld M,
Ward J,
Rehg J,
Waldmann T,
Jaffe E,
Roopenian DC,
Morse H.
IL-21-Driven Neoplasms in SJL Mice Mimic Some Key Features of Human Angioimmunoblastic T-Cell Lymphoma. Am J Pathol 2015 Nov; 185(11):3102-14.