Journal
JOURNAL OF MEDICAL PRIMATOLOGY
Volume 49, Issue 1, Pages 26-33Publisher
WILEY
DOI: 10.1111/jmp.12438
Keywords
B-cell lymphoma 6; germinal center reaction; lymphoid hyperplasia; T follicular helper
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Funding
- The Philadelphia Foundation
- Commonwealth of Pennsylvania
- Commonwealth Universal Research Enhancement Program, Pennsylvania Department of Health
- Ken Nimblett and the Summerhill Trust
- Penn Center for AIDS Research [P30CA010815]
- National Institutes of Health (NIH) [S10OD019964]
- NIAID
- NIMH
- NINDS
- NIDA [UM1AI126620]
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Background The BTB domain of B-cell lymphoma 6 (BCL6) protein was identified as a therapeutic target for B-cell lymphoma. This study compared the pharmacokinetics (PK) of the BCL6 BTB inhibitor (FX1) between mice and macaques, as well as evaluating its lymphoid suppressive effect in uninfected macaques with lymphoid hyperplasia. Materials and Methods Eight uninfected adult Indian rhesus macaques (Macaca mulatta) were used in the study, four animals carrying lymphoid tissue hyperplasia. Plasma FX1 levels were measured by HPLC-MS/MS. Lymph node biopsies were used for H&E and immunohistochemistry staining, as well as mononuclear cell isolation for flow cytometry analysis. Results Inhibition of the BCL6 BTB domain with FX1 led to a reduction in the frequency of GC, Tfh CD4(+), and Tfh precursor cells, as well as resolving lymphoid hyperplasia, in rhesus macaques. Conclusions B-cell lymphoma 6 inhibition may represent a novel strategy to reduce hyperplastic lymphoid B-cell follicles and decrease Tfh cells.
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