免疫学

曾文文

清华大学医学院教授

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探索能量平衡网络,开发神经免疫代谢稳态重塑策略

曾文文,于清华大学获学士学位,美国德州大学西南医学中心获博士学位,美国基因泰克公司和洛克菲勒大学完成博士后研究。现为清华大学医学院长聘教授,博士生导师,慢性疾病的免疫学研究北京市重点实验室副主任。曾获国家自然科学基金委“杰出青年科学基金”、“优秀青年科学基金”、求是基金会杰出青年科学家奖等。担任AJP-Endo 和Molecular Immunology杂志副主编,Protein & Cell、Science Bulletin、Advanced Science、Journal of Genetics and Genomics、Oxford Open Immunology等杂志编委。科研方向为脑-体链接的生理和相关病理机制,着重研究交感神经、感觉神经的支配、功能和紊乱,探索免疫和神经系统参与代谢的重要功能,促进基于神经免疫干预重塑代谢的策略研发。

能量稳态和疾病研究,开发基于神经和免疫调控网络的分子药物

曾文文研究团队致力于利用免疫学、神经生物学等最新手段,深度解析能量平衡的生理基础和病理机制,通过发现重要基因和分子节点发展靶向神经免疫重塑的保护和干预策略。同时通过研究宿主的天然免疫保护激活和抑制机理,发展基于宿主免疫的感染、炎症调控药物和保护策略。

研究团队揭示了神经系统对损伤和危险信号的识别和应答途径,同时阐明了神经调控外周脂肪代谢的基础和机理。研究在领域内首次实现了白色脂肪组织的全组织免疫荧光染色结合三维荧光光片成像体系,在单纤维分辨率水平建立了神经在脂肪组织中的分布图谱和空间联系,阐明了神经在脂肪代谢过程中的重要功能。揭示白色脂肪组织中多系统的分布及功能不仅对阐释脂肪组织局部代谢和免疫稳态,同时对进一步理解机体整体水平多系统、多细胞的协同作用机制、动态调节和代谢重塑有重要意义。研究成果推动了对代谢中神经调控机制的深入认识,为肥胖症、糖尿病、感染、神经病理痛等病理过程和发展中的神经基础拓宽了理解,为发展基于神经活动的新型手段提供了新的思路。

1. Ren, W., Chen, J., Wang, W., Li, Q., Yin, X., Zhuang, G., Zhou, H.#, Zeng, W.# (2024) Sympathetic nerve-enteroendocrine L cell communication modulates GLP-1 release, brain glucose utilization, and cognitive function. Neuron.

2. Ren, W.*, Hua, M.*, Cao, F.#, Zeng, W.# (2023) The sympathetic-immune milieu in metabolic health and diseases: insights from pancreas, liver, intestine and adipose tissues. Adv Sci.

3. Wan, Y. and Zeng, W.# (2023) Neural innervation and regulation of adipose tissue. Progress in Physiological Sciences.

4. Sun, M. *, Wan, Y. *, Sun, M. *, Meng, Z. #, Zeng, W. # (2023) Neural innervation in adipose tissue, gut, pancreas, and liver. Life Metabolism.

5. Zhang, S., Chen, J., Li, Q., and Zeng, W.# (2023) Opioid growth factor receptor promotes adipose tissue thermogenesis via enhancing lipid oxidation. Life Metabolism. 2(3).

6. Zhang, T.*#, Qian, X.*, Zeng, W.#, and Wei, B.# (2023) Custom folding of double-stranded DNA directed by triplex formation. Chem. 9(6): 1507-1517.

7. Li, Q., and Zeng, W.# (2023) Sensing and acting: Full circle in fat. Cell Metab. 35(1):9-11.

8. Jiang, M., and Zeng, W.# (2023) Antiviral immunity rewired for axon regeneration. Cell Rep Med. 4(1):100907.

9. Meng, X., Chen J. #, and Zeng, W.# (2022) Stromal cell-derived NGF controls sympathetic innervation in subcutaneous fat. J Lipid Res. 100264.

10. Ding, X., Chen J., and Zeng, W.# (2022) Neuroimmune regulation in the pancreas. Fundamental Research.

11. Guo, Z., Yang, H., Zhang, J.R., Zeng, W.#, and Hu, X.# (2022) Leptin receptor signaling sustains metabolic fitness of alveolar macrophages to attenuate pulmonary inflammation. Sci Adv 8(28).

12. Zeng, W.#, Yang, F.#, Shen, W.#, Zhan, C.#, Zheng, P.#, and Hu, J. (2022) Interactions between central nervous system and peripheral metabolic organs, Science China Life Sciences. doi: 10.1007/s11427-021-2103-5.

13. Xie, H., Heier, C., Meng, X., Bakiri, L., Pototschnig, I., Tang, Z., Schauer, S., Baumgartner, V.J., Grabner, G.F., Schabbauer, G., Wolinski, H., Robertsong, G.R., Hoefler, G., Zeng, W., Wagner, E.F., Schweiger, M.#, and Zechner, R.# (2022) An Immune-Sympathetic Neuron Communication Axis Guides Adipose Tissue Browning in Cancer-associated Cachexia, Proc Natl Acad Sci U S A. 119(9).

14. Meng, X.*, Qian, X.*, Ding, X.*, Wang, W.*, Yin, X.#, Zhuang, G.#, and Zeng, W.# (2022) Eosinophils regulate intra-adipose axonal plasticity, Proc Natl Acad Sci U S A. 119(3).

15. Zeng, W.#, and Qian, X. (2021) Neuronal Regulation of Adipose Tissue Biology in Neuron Signaling in Metabolic Regulation (Tong, Q., ed), CRC Press.

16. Qian, X., Meng, X., Zhang, S., and Zeng, W.# (2021) Neuroimmune regulation of white adipose tissues. FEBS J. 10.1111/febs.16213.

17. Meng, X., and Zeng, W.# (2021) Fat mesenchyme closes the neural-ILC2 circuit, Immunity. 54, 2191-2193.

18. Zhuo, W.#, Zhou, H., Guo, R., Yi, J., Zhang, L., Yu, L., Sui, Y., Zeng, W., Wang, P.#, and Yang, M.# (2021) Structure of intact human MCU supercomplex with the auxiliary MICU subunits, Protein Cell. 12, 220-229.

19. Zhang, S., Zhou, J., Zhang, Y., Liu, T., Friedel, P., Zhuo, W., Somasekharan, S., Roy, K., Zhang, L., Liu, Y., Meng, X., Deng, H., Zeng, W., Li, G.#, Forbush, B.#, and Yang, M.# (2021) The structural basis of function and regulation of neuronal cotransporters NKCC1 and KCC2, Commun Biol. 4, 226.

20. Sui, Y., and Zeng, W.# (2020) MS4A4A Regulates Arginase 1 Induction during Macrophage Polarization and Lung Inflammation in Mice, Eur J Immunol. 50, 1602-1605.

21. Meng, X., Zeng, W., Young, S. G.#, and Fong, L. G. (2020) GPIHBP1, a partner protein for lipoprotein lipase, is expressed only in capillary endothelial cells, J Lipid Res. 61, 591.

22. Hu, Z.*, Deng, N.*, Liu, K., Zhou, N., Sun, Y., and Zeng, W.# (2020) CNTF-STAT3-IL-6 Axis Mediates Neuroinflammatory Cascade across Schwann Cell-Neuron-Microglia, Cell Rep. 31, 107657.

23. Hu, Z., Deng, N., Liu, K., and Zeng, W.# (2019) DLK mediates the neuronal intrinsic immune response and regulates glial reaction and neuropathic pain, Exp Neurol. 322, 113056.

24. Wang, Q.*, Zhang, S.*, Liu, T.*, Wang, H., Liu, K., Wang, Q., and Zeng, W.# (2018) Sarm1/Myd88-5 Regulates Neuronal Intrinsic Immune Response to Traumatic Axonal Injuries, Cell Rep. 23, 716-724.

25. Hu, Z., and Zeng, W.# (2018). Splenic Leukocytes Get the Nerves up for Myelopoiesis. Immunity 49, 1-3.

26. Zhang, S.*, Li, N.*, Zeng, W., Gao, N.#, and Yang, M.# (2017). Cryo-EM structures of the mammalian endo-lysosomal TRPML1 channel elucidate the combined regulation mechanism. Protein Cell 8, 834-847.

27. Jiang, H.*, Ding, X.*, Cao, Y., Wang, H., and Zeng, W.# (2017). Dense Intra-adipose Sympathetic Arborizations Are Essential for Cold-Induced Beiging of Mouse White Adipose Tissue. Cell Metab 26, 686-692 e683.

28. Zeng, W.*, Pirzgalska, R.M.*, Pereira, M.M., Kubasova, N., Barateiro, A., Seixas, E., Lu, Y.H., Kozlova, A., Voss, H., Martins, G.G., et al. (2015). Sympathetic neuro-adipose connections mediate leptin-driven lipolysis. Cell 163, 84-94.

29. Zeng, W.*, Lu, Y.H.*, Lee, J., and Friedman, J.M. # (2015). Reanalysis of parabiosis of obesity mutants in the age of leptin. Proc Natl Acad Sci U S A 112, E3874-3882.

30. Peng, Y.*, Zeng, W.*, Ye, H., Han, K.H., Dharmarajan, V., Novick, S., Wilson, I.A., Griffin, P.R., Friedman, J.M., and Lerner, R.A.# (2015). A General Method for Insertion of Functional Proteins within Proteins via Combinatorial Selection of Permissive Junctions. Chem Biol 22, 1134-1143.

31. Glasmacher, E.*, Agrawal, S.*, Chang, A.B.*, Murphy, T.L.*, Zeng, W.*, Vander Lugt, B., Khan, A.A., Ciofani, M., Spooner, C.J., Rutz, S., et al. (2012). A genomic regulatory element that directs assembly and function of immune-specific AP-1-IRF complexes. Science 338, 975-980.

32. Rutz, S., Noubade, R., Eidenschenk, C., Ota, N., Zeng, W., Zheng, Y., Hackney, J., Ding, J., Singh, H., and Ouyang, W.# (2011). Transcription factor c-Maf mediates the TGF-beta-dependent suppression of IL-22 production in T(H)17 cells. Nat Immunol 12, 1238-1245.

33. Zeng, W.*, Sun, L.*, Jiang, X., Chen, X., Hou, F., Adhikari, A., Xu, M., and Chen, Z.J.# (2010). Reconstitution of the RIG-I pathway reveals a signaling role of unanchored polyubiquitin chains in innate immunity. Cell 141, 315-330.

34. Zeng, W., Xu, M., Liu, S., Sun, L.#, and Chen, Z.J.# (2009). Key role of Ubc5 and lysine-63 polyubiquitination in viral activation of IRF3. Mol Cell 36, 315-325.

35. Xu, M., Skaug, B., Zeng, W., and Chen, Z.J.# (2009). A ubiquitin replacement strategy in human cells reveals distinct mechanisms of IKK activation by TNFalpha and IL-1beta. Mol Cell 36, 302-314.

36. Xia, Z.P., Sun, L., Chen, X., Pineda, G., Jiang, X., Adhikari, A., Zeng, W., and Chen, Z.J.# (2009). Direct activation of protein kinases by unanchored polyubiquitin chains. Nature 461, 114-119.

37. Zeng, W., and Chen, Z.J.# (2008). MITAgating viral infection. Immunity 29, 513-515.

38. Yang, M., Xu, G., Li, S., Sun, L., Shi, N., Zeng, W., Pang, H., Zhang, W., and Rao, Z.# (2003). Crystallization and preliminary crystallographic analysis of the extracellular fragment of FcalphaRI/CD89. Acta Crystallogr D Biol Crystallogr 59, 2251-2253.

39. Sun, Z.H., Lai, Y.L., Zeng, W., Zhao, D., Zuo, H.C., and Xie, Z.P.# (2003). Neural stem/progenitor cells survive and differentiate better in PD rats than in normal rats. Acta Neurochir Suppl 87, 169-174.

40. Sun, Z.H., Lai, Y.L., Zeng, W., Zhao, D., Ye, Z.W., Zuo, H.C., and Xie, Z.P.# (2003). Mesencephalic progenitors can improve rotational behavior and reconstruct nigrostriatal pathway in PD rats. Acta Neurochir Suppl 87, 175-180.

学术荣誉与奖励

基金委杰出青年基金

基金委优秀青年基金

生物物理学会脂质代谢与生物能学分会青年科学家奖

求是基金会杰出青年科学家奖

国家青年人才基金

开设课程

实验免疫学的方法学

免疫信号转导与疾病

病原生物与免疫学进展

免疫学-肿瘤免疫

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