Antigen presentation safeguards the integrity of the hematopoietic stem cell pool.
Antigen presentation safeguards the integrity of the hematopoietic stem cell pool.
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抗原表现保护造血干细胞库的完整性。
DOI：
10.1016/j.stem.2022.04.007
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发表时间：
2022-05-05
期刊：
影响因子：
23.9
通讯作者：
Haas, Simon
中科院分区：
文献类型：
--
作者：
Hernandez-Malmierca, Pablo;Vonficht, Dominik;Schnell, Alexandra;Uckelmann, Hannah J.;Bollhagen, Alina;Mahmoud, Mohamed A. A.;Landua, Sophie-Luise;van der Salm, Elise;Trautmann, Christine L.;Raffel, Simon;Gruenschlaeger, Florian;Lutz, Raphael;Ghosh, Michael;Renders, Simon;Correia, Nadia;Donato, Elisa;Dixon, Karin O.;Hirche, Christoph;Andresen, Carolin;Robens, Claudia;Werner, Paula S.;Boch, Tobias;Eisel, David;Osen, Wolfram;Pilz, Franziska;Przybylla, Adriana;Klein, Corinna;Buchholz, Frank;Milsom, Michael D.;Essers, Marieke A. G.;Eichmueller, Stefan B.;Hofmann, Wolf-Karsten;Nowak, Daniel;Huebschmann, Daniel;Hundemer, Michael;Thiede, Christian;Bullinger, Lars;Mueller-Tidow, Carsten;Armstrong, Scott A.;Trumpp, Andreas;Kuchroo, Vijay K.;Haas, Simon
造血干细胞和祖细胞（HSPC）负责产生血液和免疫细胞。在整个生命过程中，HSPC获得可导致血液癌症的致癌畸变。虽然已经确定了维持干细胞完整性的分子程序，但从干细胞库中消除恶性HSPC的安全机制仍然缺乏表征。在这里，我们表明，HSPCs组成型通过主要组织相容性复合体II类抗原。在恶性转化期间发生的免疫原性抗原的呈递触发HSPC和抗原特异性CD4+ T细胞之间的双向相互作用，引起异常HSPC的干细胞增殖、分化和特异性耗竭。这种免疫监视机制有效地从造血系统中消除转化的HSPC，从而预防白血病发作。总之，我们的数据揭示了HSPC和CD4+ T细胞之间的双向相互作用，表明HSPC不仅是免疫信号的被动接收者，而且积极参与适应性免疫反应，以保护干细胞库的完整性。哈斯及其同事证明造血干细胞（HSC）作为抗原呈递细胞。免疫原性抗原的呈递触发与抗原特异性CD4+ T细胞的双向相互作用，导致患病HSC的快速耗尽，从而保护干细胞库的完整性。
Hematopoietic stem and progenitor cells (HSPCs) are responsible for the production of blood and immune cells. Throughout life, HSPCs acquire oncogenic aberrations that can cause hematological cancers. While molecular programs maintaining stem cell integrity have been identified, safety mechanisms eliminating malignant HSPCs from the stem cell pool remain poorly characterized. Here we show that HSPCs constitutively present antigens via major histocompatibility complex class II. The presentation of immunogenic antigens, as occurring during malignant transformation, triggers bidirectional interactions between HSPCs and antigen-specific CD4+ T cells, causing stem cell proliferation, differentiation and specific exhaustion of aberrant HSPCs. This immunosurveillance mechanism effectively eliminates transformed HSPCs from the hematopoietic system, thereby preventing leukemia onset. Together, our data reveal a bidirectional interaction between HSPCs and CD4+ T cells, demonstrating that HSPCs are not only passive receivers of immunological signals, but actively engage in adaptive immune responses to safeguard the integrity of the stem cell pool. Haas and colleagues show that hematopoietic stem cells (HSCs) act as antigen presenting cells. The presentation of immunogenic antigens triggers a bidirectional interaction with antigen-specific CD4+ T cells, resulting in the rapid exhaustion of diseased HSCs, thereby safeguarding the integrity of the stem cell pool.
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影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
DOI：
10.1056/nejmoa1409405
发表时间：
2014-12-25
期刊：
The New England journal of medicine
影响因子：
--
作者：
Genovese G;Kähler AK;Handsaker RE;Lindberg J;Rose SA;Bakhoum SF;Chambert K;Mick E;Neale BM;Fromer M;Purcell SM;Svantesson O;Landén M;Höglund M;Lehmann S;Gabriel SB;Moran JL;Lander ES;Sullivan PF;Sklar P;Grönberg H;Hultman CM;McCarroll SA
通讯作者：
McCarroll SA
影响因子：
11.4
作者：
Costello, RT;Mallet, F;Olive, D
通讯作者：
Olive, D
影响因子：
2.7
作者：
Dhaliwal, J. S.;Wong, Lily;Murad, Shahnaz
通讯作者：
Murad, Shahnaz
影响因子：
4
作者：
Barnden, MJ;Allison, J;Carbone, FR
通讯作者：
Carbone, FR