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.
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.
Jain, Shweta; Chen, Jing; Nicolae, Alina; Wang, Hongsheng; Shin, Dong-Mi; Adkins, Elisabeth B.; Sproule, Thomas J.; Leeth, Caroline M; Sakai, Tomomi; Kovalchuk, Alexander L; Raffeld, Mark; Ward, Jerrold M; Rehg, Jerold E; Waldmann, Thomas A; Jaffe, Elaine S; Roopenian, Derry C.; and Morse, Herbert C, "IL-21-Driven Neoplasms in SJL Mice Mimic Some Key Features of Human Angioimmunoblastic T-Cell Lymphoma." (2015). Faculty Research 2015. 195.