IL-21-driven neoplasms in SJL mice mimic some key features of human angioimmunoblastic T-cell lymphoma.

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; Morse, Herbert C (2015). IL-21-driven neoplasms in SJL mice mimic some key features of human angioimmunoblastic T-cell lymphoma. American journal of pathology, 185(11), pp. 3102-3114. Elsevier 10.1016/j.ajpath.2015.07.021

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

Nicolae, Alina

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

0002-9440

Publisher:

Elsevier

Language:

English

Submitter:

Ekkehard Hewer

Date Deposited:

20 Apr 2017 14:50

Last Modified:

20 Apr 2017 14:50

Publisher DOI:

10.1016/j.ajpath.2015.07.021

PubMed ID:

26363366

BORIS DOI:

10.7892/boris.95942

URI:

https://boris.unibe.ch/id/eprint/95942

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