Modeling human T1D-associated autoimmune processes.
Modeling human T1D-associated autoimmune processes.
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DOI：
10.1016/j.molmet.2021.101417
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发表时间：
2022-03
影响因子：
8.1
通讯作者：
Creusot RJ
中科院分区：
文献类型：
--
作者：
Khosravi-Maharlooei M;Madley R;Borsotti C;Ferreira LMR;Sharp RC;Brehm MA;Greiner DL;Parent AV;Anderson MS;Sykes M;Creusot RJ
Type 1 diabetes (T1D) is an autoimmune disease characterized by impaired immune tolerance to β-cell antigens and progressive destruction of insulin-producing β-cells. Animal models have provided valuable insights for understanding the etiology and pathogenesis of this disease, but they fall short of reflecting the extensive heterogeneity of the disease in humans, which is contributed by various combinations of risk gene alleles and unique environmental factors. Collectively, these factors have been used to define subgroups of patients, termed endotypes, with distinct predominating disease characteristics. Here, we review the gaps filled by these models in understanding the intricate involvement and regulation of the immune system in human T1D pathogenesis. We describe the various models developed so far and the scientific questions that have been addressed using them. Finally, we discuss the limitations of these models, primarily ascribed to hosting a human immune system (HIS) in a xenogeneic recipient, and what remains to be done to improve their physiological relevance. To understand the role of genetic and environmental factors or evaluate immune-modifying therapies in humans, it is critical to develop and apply models in which human cells can be manipulated and their functions studied under conditions that recapitulate as closely as possible the physiological conditions of the human body. While microphysiological systems and living tissue slices provide some of these conditions, HIS mice enable more extensive analyses using in vivo systems.
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影响因子：
12.8
作者：
Khosravi-Maharlooei M;Li H;Hoelzl M;Zhao G;Ruiz A;Misra A;Li Y;Teteloshvili N;Nauman G;Danzl N;Ding X;Pinker EY;Obradovic A;Yang YG;Iuga A;Creusot RJ;Winchester R;Sykes M
通讯作者：
Sykes M
影响因子：
16.6
作者：
Bautista JL;Cramer NT;Miller CN;Chavez J;Berrios DI;Byrnes LE;Germino J;Ntranos V;Sneddon JB;Burt TD;Gardner JM;Ye CJ;Anderson MS;Parent AV
通讯作者：
Parent AV
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
7.7
作者：
Ahmed, Simi;Cerosaletti, Karen;Brusko, Todd M.
通讯作者：
Brusko, Todd M.
影响因子：
4.8
作者：
Brehm, Michael A.;Kenney, Laurie L.;Shultz, Leonard D.
通讯作者：
Shultz, Leonard D.