长聘教轨副教授
炎症反应可保护人体免受病原体的入侵及外界刺激的伤害，通常可自行消退。然而在特定条件下，炎症消退过程被抑制，急性炎症发展为慢性炎性疾病，经久不愈。组织特异性稳态分子可在微环境中调节免疫细胞的丰度及功能，主动促进炎症的消退，最终恢复/维持组织的完整性和稳态。然而，迄今发现的主动促进炎症消退的组织特异性稳态分子数量十分有限，亟需深入探索。
在多种慢性疾病并存的情况下，对单一疾病的治疗很难达到理想的效果。 因此，在单一炎症的研究基础上，深入解析慢性并发症的致病机制并确定关键致病因子，将为慢性并发症的治疗提供新的治疗思路和靶标。课题组的前期工作明确了炎性信号诱导的造血干细胞水平的训练免疫在慢性并发症发病中的重要作用。因此，本课题组致力于开发同时针对外周炎症及骨髓中训练免疫的联合疗法，从而有效地抑制外周炎症与骨髓之间的有害反馈回路，限制慢性并发症的进展。
表观遗传修饰在骨髓造血干细胞的分化与命运决定中发挥了关键作用。 课题组前期研究结果表明外周炎性信号可显著调控HSPC中表观遗传修饰介导的训练免疫的形成。课题组将对外周炎性信号诱导下，HSPC内多种组蛋白修饰及mRNA的m6A甲基化修饰在全基因水平的分布变化进行分析，鉴定受表观修饰调控的关键骨髓髓系分化及炎性相关基因及其重要表观修饰位点，为抑制造血干细胞水平训练免疫的形成提供关键靶点。
Xiaofei Li*, Hui Wang*, Xiang Yu, Gundappa Saha, Lydia Kalafati, Charalampos Ioannidis, Ioannis Mitroulis, Mihai G Netea, Triantafyllos Chavakis, George Hajishengallis. Maladaptive innate immune training of myelopoiesis links inflammatory comorbidities. Cell, 2022 May 12;185(10):1709-1727.e18.
Ioannis Kourtzelis*, Xiaofei Li*, Ioannis Mitroulis, Daniel Grosser, Tetsuhiro Kajikawa, Baomei Wang, Michal Grzybek, Janusz Von Renesse, Aleksander Czogalla, Maria Troullinaki, Anaisa Ferreira, Christian Doreth, Klara Ruppova, Lan-Sun Chen, Kavita Hosur, Jong-Hyung Lim, Kyoung-Jin Chung, Sylvia Grossklaus, Anne Kathrin Tausche, Leo AB Joosten, Niki M Moutsopoulos, Ben Wielockx, Antonio Castrillo, Jonathan M Korostoff, Ünal Coskun, George Hajishengallis, Triantafyllos Chavakis. DEL-1 promotes macrophage efferocytosis and clearance of inflammation. Nat. Immunol. 2019 Jan;20(1):40-49.
Xiaofei Li*, Alessandra Colamatteo*, Lydia Kalafati, Tetsuhiro Kajikawa, Hui Wang, Jong-Hyung Lim, Khalil Bdeir, Kyoung-Jin Chung, Xiang Yu, Clorinda Fusco, Antonio Porcellini, Salvatore De Simone, Giuseppe Matarese, Triantafyllos Chavakis, Veronica De Rosa, George HajishengallisThe DEL-1/β3 integrin axis promotes regulatory T cell responses during inflammation resolution. J Clin Invest. 2020 Dec 1; 130(12): 6261–6277.
George Hajishengallis#, Xiaofei Li#, Triantafyllos Chavakis#. Immunometabolic control of hematopoiesis. Mol. Asp. Med. 2021 Feb;77:100923.
Lydia Kalafati, Ioannis Kourtzelis, Jonas Schulte-Schrepping, Xiaofei Li, Aikaterini Hatzioannou, Tatyana Grinenko, Eman Hagag, Anupam Sinha, Canan Has, Sevina Dietz, Antonio Miguel de Jesus Domingues, Marina Nati, Sundary Sormendi, Ales Neuwirth, Antonios Chatzigeorgiou, Athanasios Ziogas, Mathias Lesche, Andreas Dahl, Ian Henry, Pallavi Subramanian, Ben Wielockx, Peter Murray, Peter Mirtschink, Kyoung-Jin Chung, Joachim L Schultze, Mihai G Netea, George Hajishengallis, Panayotis Verginis, Ioannis Mitroulis, Triantafyllos Chavakis. Innate immune training of granulopoiesis promotes anti-tumor activity. Cell. 2020 Oct 29;183(3):771-785.e12.
Hui Wang, Xiaofei Li, Tetsuhiro Kajikawa, Jieun Shin, Jong-Hyung Lim, Ioannis Kourtzelis, Kosuke Nagai, Jonathan M Korostoff, Sylvia Grossklaus, Ronald Naumann, Triantafyllos Chavakis, George Hajishengallis. Stromal cell–derived DEL-1 inhibits Tfh cell activation and inflammatory arthritis. J. Clin. Investig. 2021 Oct 1;131(19):e150578.
Da-Yo Yuh, Tomoki Maekawa, Xiaofei Li, Tetsuhiro Kajikawa, Khalil Bdeir, Triantafyllos Chavakis, George Hajishengallis. The secreted protein DEL-1 activates a β3 integrin–FAK–ERK1/2–RUNX2 pathway and promotes osteogenic differentiation and bone regeneration. J. Biol. Chem. 2020 May 22;295(21):7261-7273.
论文下载
支撑材料