Remy Bosselut, M.D., Ph.D.
- Center for Cancer Research
- National Cancer Institute
- Building 37, Room 3032A
- Bethesda, MD 20892-4259
Our lab's focus is on the transcriptional control of CD4+ T cell development and function. We are specifically interested in the transcriptomic programs controlling the emergence of CD4+ lineage in the thymus and in the transcriptional control of CD4+ T cell responses to pathogens and tumors.
Areas of Expertise
1) T lymphocyte 2) T cell development 3) T cell effector differentiation 4) transcription 5) chromatin
Our lab focuses on the transcriptional control of T cell development and function. We are specifically interested in the transcriptomic programs controlling the emergence of CD4+ lineage in the thymus and in the transcriptional control of CD4+ T cell responses to pathogens and tumors.
We study the differentiation and function of T lymphocytes (T cells), including CD4+ helper T cells. T are essential for immune responses and CD4+ T cells control most aspects of the immune response, through cytokine secretion or direct cell-cell interactions. In addition, CD4+ T cells are involved in tumor control and clinical studies have established their potential as anti-tumor agents. The laboratory addresses these questions by integrating multiple approaches, including biochemical analyses to understand transcription factor function (1), ex vivo genetics and cell transplantation (1, 2), and bioinformatics (3). Current research focuses on three key areas.
1- CD4+ helper T cell development in the thymus. CD4+ T cells differentiate in the thymus from CD4+CD8+ “double-positive” precursors (thymocytes). The laboratory has a long-standing interest in the signals and transcription factors that direct CD4+ T cell development and their transcription factor targets (4). Recent and ongoing research investigates how the transcriptomic and epigenomic program characteristic of CD4+ T cells is established in these precursors, leveraging high-throughput gene expression and chromatin accessibility analyses (including single-cell RNA and ATAC sequencing (3).
2-Control of CD4+ T cell responses to infection and tumors. Using single-cell RNAseq and ATACseq, we recently characterized CD4+ T cell responses to infection (5, 6) or tumors (7). Current research aims at developing experimental models to understand the function of CD4+ T cells in tumors and to design strategies to harness their anti-tumor potential.
3-Role of the thymus in immune tolerance. Maintaining immune homeostasis, including tolerance to self-antigens and commensals at mucosal barriers, is a critical function of T cells. Recent (3 , 8). Ongoing studies investigate now the thymus contributes to tolerance through the deletion of self-reactive T cell precursors and generation of T cells with immunoregulatory functions.
1. Y. Gao et al., NuRD complex recruitment to Thpok mediates CD4(+) T cell lineage differentiation. Sci Immunol 7, eabn5917 (2022).
2. M. S. Vacchio et al., A Thpok-Directed Transcriptional Circuitry Promotes Bcl6 and Maf Expression to Orchestrate T Follicular Helper Differentiation. Immunity 51, 465-478.e466 (2019).
3. L. B. Chopp et al., An Integrated Epigenomic and Transcriptomic Map of Mouse and Human αβ T Cell Development. Immunity 53, 1182-1201.e1188 (2020).
4. G. Sun et al., The zinc finger protein cKrox directs CD4 lineage differentiation during intrathymic T cell positive selection. Nat Immunol 6, 373-381 (2005).
5. T. Ciucci et al., The Emergence and Functional Fitness of Memory CD4(+) T Cells Require the Transcription Factor Thpok. Immunity 50, 91-105.e104 (2019).
6. T. Ciucci et al., Dependence on Bcl6 and Blimp1 drive distinct differentiation of murine memory and follicular helper CD4+ T cells. J Exp Med 219, (2022).
7. A. Magen et al., Single-Cell Profiling Defines Transcriptomic Signatures Specific to Tumor-Reactive versus Virus-Responsive CD4(+) T Cells. Cell Rep 29, 3019-3032.e3016 (2019).
8. J. Nie et al., The transcription factor LRF promotes integrin β7 expression by and gut homing of CD8αα(+) intraepithelial lymphocyte precursors. Nat Immunol 23, 594-604 (2022).
The Emergence and Functional Fitness of Memory CD4(+) T Cells Require the Transcription Factor Thpok
How T Cells Recycle the CD4+-CD8+ Lineage Commitment Transcriptional Circuitry To Control Their Function
Remy Bosselut, M.D., Ph.D.
Dr. Remy Bosselut trained at the Institut Curie in Paris, France. He earned his M.D. degree in 1992 from the Xavier Bichat School of Medicine and his Ph.D. degree in 1993 from the University Denis Diderot, both in Paris. Dr. Bosselut obtained postdoctoral training at the NCI Experimental Immunology Branch and joined the Laboratory of Immune Cell Biology in 2000.
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