IL-21-driven neoplasms in SJL mice mimic some key features of human angioimmunoblastic T-cell lymphoma
| Autor: | Tomomi Sakai, Herbert C. Morse, Alina Nicolae, Derry C. Roopenian, Caroline M. Leeth, Jing Chen, Dong-Mi Shin, Jerold E. Rehg, Shweta Jain, Elaine S. Jaffe, Mark Raffeld, Alexander L. Kovalchuk, Elisabeth B Adkins, Thomas A. Waldmann, Jerrold M. Ward, Hongsheng Wang, Thomas J. Sproule |
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| Rok vydání: | 2015 |
| Předmět: |
CD4-Positive T-Lymphocytes
Angioimmunoblastic T-cell lymphoma Lymphoma B-Cell Microarray Spleen Biology Lymphoma T-Cell Immunoglobulin G Pathology and Forensic Medicine Mice medicine Animals Humans Oligonucleotide Array Sequence Analysis B-Lymphocytes Gene Expression Profiling Interleukins Germinal center Interleukin-21 Receptor alpha Subunit Regular Article Sequence Analysis DNA medicine.disease Germinal Center Lymphoma Gene expression profiling Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure Interleukin-21 receptor Immunoblastic Lymphadenopathy Immunology biology.protein Cytokines Female Lymph Nodes Signal Transduction |
| Zdroj: | The American journal of pathology. 185(11) |
| ISSN: | 1525-2191 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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