IL-21-driven neoplasms in SJL mice mimic some key features of human angioimmunoblastic T-cell lymphoma.
Fiche publication
Date publication
novembre 2015
Journal
The American journal of pathology
Auteurs
Membres identifiés du Cancéropôle Est :
Dr NICOLAE Alina
Tous les auteurs :
Jain S, Chen J, Nicolae A, Wang H, Shin DM, Adkins EB, Sproule TJ, Leeth CM, Sakai T, Kovalchuk AL, Raffeld M, Ward JM, Rehg JE, Waldmann TA, Jaffe ES, Roopenian DC, Morse HC
Lien Pubmed
Résumé
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.
Mots clés
Animals, B-Lymphocytes, pathology, CD4-Positive T-Lymphocytes, pathology, Cytokines, blood, Disease Models, Animal, Female, Gene Expression Profiling, Germinal Center, pathology, Humans, Immunoblastic Lymphadenopathy, pathology, Immunoglobulin G, blood, Interleukin-21 Receptor alpha Subunit, genetics, Interleukins, genetics, Lymph Nodes, pathology, Lymphoma, B-Cell, pathology, Lymphoma, T-Cell, pathology, Mice, Mice, Inbred C57BL, Oligonucleotide Array Sequence Analysis, Sequence Analysis, DNA, Signal Transduction, Spleen, pathology
Référence
Am J Pathol. 2015 Nov;185(11):3102-14