Integrated Metabolomics and Proteomics Analyses in the Local Milieu of Islet Allografts in Rejection versus Tolerance.
Integrated Metabolomics and Proteomics Analyses in the Local Milieu of Islet Allografts in Rejection versus Tolerance.
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DOI：
10.3390/ijms22168754
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发表时间：
2021-08-15
影响因子：
5.6
通讯作者：
Abdulreda MH
中科院分区：
文献类型：
--
作者：
Hernandez LF;Betancourt LR;Nakayasu ES;Ansong C;Ceballos GA;Paredes D;Abdulreda MH
了解导致同种异体胰岛移植物排斥与耐受的免疫机制是至关重要的，因为它有助于开发创新方法来改善移植结果。在这里，我们使用我们建立的眼内胰岛移植模型，以获得新的见解，在局部代谢组和蛋白质组的变化胰岛同种异体移植物的直接微环境与免疫介导的排斥或耐受。我们在代表每个移植结果下移植物微环境的房水样本中进行了综合代谢组学和蛋白质组学分析。结果表明，与瓦尔堡效应相关的几种游离氨基酸、小伯胺和可溶性蛋白质上调或下调与任一结果相关。一般而言，观察到的与排斥反应相关的局部代谢物和蛋白质谱的变化与已建立的促炎代谢途径一致，观察到的与耐受性相关的变化是免疫调节性的。综上所述，目前的研究结果进一步支持免疫细胞的代谢重编程对免疫调节的潜力，通过针对特定代谢途径的靶向药理学和饮食干预，促进瓦尔堡效应，以防止移植胰岛的排斥反应，并促进其免疫耐受。
An understanding of the immune mechanisms that lead to rejection versus tolerance of allogeneic pancreatic islet grafts is of paramount importance, as it facilitates the development of innovative methods to improve the transplant outcome. Here, we used our established intraocular islet transplant model to gain novel insight into changes in the local metabolome and proteome within the islet allograft’s immediate microenvironment in association with immune-mediated rejection or tolerance. We performed integrated metabolomics and proteomics analyses in aqueous humor samples representative of the graft’s microenvironment under each transplant outcome. The results showed that several free amino acids, small primary amines, and soluble proteins related to the Warburg effect were upregulated or downregulated in association with either outcome. In general, the observed shifts in the local metabolite and protein profiles in association with rejection were consistent with established pro-inflammatory metabolic pathways and those observed in association with tolerance were immune regulatory. Taken together, the current findings further support the potential of metabolic reprogramming of immune cells towards immune regulation through targeted pharmacological and dietary interventions against specific metabolic pathways that promote the Warburg effect to prevent the rejection of transplanted islets and promote their immune tolerance.
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影响因子：
3.7
作者：
Ceballos GA;Hernandez LF;Paredes D;Betancourt LR;Abdulreda MH
通讯作者：
Abdulreda MH
影响因子：
1.2
作者：
Abdulreda, Midhat H.;Caicedo, Alejandro;Berggren, Per-Olof
通讯作者：
Berggren, Per-Olof
DOI：
10.1073/pnas.1105002108
发表时间：
2011-08-02
影响因子：
11.1
作者：
Abdulreda, Midhat H.;Faleo, Gaetano;Berggren, Per-Olof
通讯作者：
Berggren, Per-Olof
DOI：
10.1007/978-3-319-39824-2_2
发表时间：
2016-01-01
期刊：
PANCREATIC ISLET ISOLATION: FROM THE MOUSE TO THE CLINIC
影响因子：
--
作者：
Abdulreda, Midhat H.;Rodriguez-Diaz, Rayner;Berggren, Per-Olof
通讯作者：
Berggren, Per-Olof
丙酮酸激酶M2激活剂促进四聚体形成并抑制肿瘤发生。
影响因子：
14.8
作者：
Anastasiou, Dimitrios;Yu, Yimin;Israelsen, William J.;Jiang, Jian-Kang;Boxer, Matthew B.;Hong, Bum Soo;Tempel, Wolfram;Dimov, Svetoslav;Shen, Min;Jha, Abhishek;Yang, Hua;Mattaini, Katherine R.;Metallo, Christian M.;Fiske, Brian P.;Courtney, Kevin D.;Malstrom, Scott;Khan, Tahsin M.;Kung, Charles;Skoumbourdis, Amanda P.;Veith, Henrike;Southall, Noel;Walsh, Martin J.;Brimacombe, Kyle R.;Leister, William;Lunt, Sophia Y.;Johnson, Zachary R.;Yen, Katharine E.;Kunii, Kaiko;Davidson, Shawn M.;Christofk, Heather R.;Austin, Christopher P.;Inglese, James;Harris, Marian H.;Asara, John M.;Stephanopoulos, Gregory;Salituro, Francesco G.;Jin, Shengfang;Dang, Lenny;Auld, Douglas S.;Park, Hee-Won;Cantley, Lewis C.;Thomas, Craig J.;Heiden, Matthew G. Vander
通讯作者：
Heiden, Matthew G. Vander