| Autor: |
Chen, Jing, Nicolae, Alina, Raffeld, Mark, Jaffe, Elaine S, Rehg, Jerold E, Roopenian, Derry C, Morse, Herbert C, Waldmann, Thomas A, Sakai, Tomomi, Wang, Hongsheng, Kovalchuk, Alexander L, Jain, Shweta, Ward, Jerrold M, Sproule, Thomas J, Adkins, Elisabeth B, Leeth, Caroline M, Shin, Dong-Mi |
| Jazyk: |
angličtina |
| Rok vydání: |
2015 |
| Předmět: |
|
| DOI: |
10.7892/boris.95942 |
| 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 |
| Externí odkaz: |
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