Journal
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Volume 26, Issue 15, Pages 4268-4276Publisher
WILEY
DOI: 10.1111/jcmm.17445
Keywords
development; differentiation; iNKT cells; Pbrm1; ROR gamma t
Categories
Funding
- National Key Research and Development Program of China [2021YFA1100702]
- Natural Science Foundation of China [32170892, 82071828]
- Natural Science Foundation of Shaanxi Province [2021JQ-025]
- Project of Independent Innovative Experiment for Postgraduates in medicine in Xi'an Jiaotong University [YJSCX-2021-xx]
- Central University Basic Research Fund [sxxj032021015]
- China Postdoctoral Science Foundation [2019 M653673]
- Early Career Research Start-up Plan of Xi'an Jiaotong University
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The study reveals a novel mechanism of Pbrm1 controlling the peripheral size of iNKT cells through regulating their development and differentiation, rather than affecting their proliferation and survival.
Under static condition, the pool size of peripheral invariant natural killer T (iNKT) cells is determined by their homeostatic proliferation, survival and thymic input. However, the underlying mechanism is not fully understood. In the present study, we found that the percentage and number of iNKT cells were significantly reduced in the spleen, but not in the thymus of mice with deletion of polybromo-1 (Pbrm1) compared to wild type (WT) mice. Pbrm1 deletion did not affect iNKT cell proliferation and survival, instead significantly impaired their development from stage 1 to stage 2. Importantly, loss of Pbrm1 led to a dysfunction of ROR gamma t expression and iNKT17 cell differentiation, but not iNKT1 and iNKT2 proportion. Collectively, our study reveals a novel mechanism of Pbrm1 controlling the peripheral size of iNKT cells through regulating their development and differentiation.
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