MHC Class I Expression by Donor Hematopoietic Stem Cells Is Required to Prevent NK Cell Attack in Allogeneic, but Not Syngeneic Recipient Mice

Hirata, Yoshihiro; Li, Hao Wei; Takahashi, K.; Ishii, Hiroshi; Sykes, Megan; Fujisaki, Joji

doi:10.1371/journal.pone.0141785

Cited by 6 publications

(5 citation statements)

References 16 publications

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“…In vivo microscopy was performed as previously described (Fujisaki et al, 2011, Lo Celso et al, 2009, Hirata et al, 2015). The mice were anaesthetized with 2– 3% isoflurane and buprenorphine.…”

Section: Methodsmentioning

confidence: 99%

CD150high Bone Marrow Tregs Maintain Hematopoietic Stem Cell Quiescence and Immune Privilege via Adenosine

et al. 2018

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A crucial player in immune regulation, FoxP3 regulatory T cells (Tregs) are drawing attention for their heterogeneity and noncanonical functions. Here, we describe a Treg subpopulation that controls hematopoietic stem cell (HSC) quiescence and engraftment. These Tregs highly expressed an HSC marker, CD150, and localized within the HSC niche in the bone marrow (BM). Specific reduction of BM Tregs achieved by conditional deletion of CXCR4 in Tregs increased HSC numbers in the BM. Adenosine generated via the CD39 cell surface ectoenzyme on niche Tregs protected HSCs from oxidative stress and maintained HSC quiescence. In transplantation settings, niche Tregs prevented allogeneic (allo-) HSC rejection through adenosine and facilitated allo-HSC engraftment. Furthermore, transfer of niche Tregs promoted allo-HSC engraftment to a much greater extent than transfer of other Tregs. These results identify a unique niche-associated Treg subset and adenosine as regulators of HSC quiescence, abundance, and engraftment, further highlighting their therapeutic utility.

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Section: Methodsmentioning

confidence: 99%

CD150high Bone Marrow Tregs Maintain Hematopoietic Stem Cell Quiescence and Immune Privilege via Adenosine

et al. 2018

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“…Indeed, in mouse models of HSC transplantation, NK cells recognized nonself MHC molecules and mediated rejection of donor HSCs. [77][78][79] Innate immune cell activation and allospecific Th1 responses were significantly attenuated, and development of lethal GVHD was reduced in mice when BM donors or recipients lacked TLR4. 80 BM-resident macrophages play a key role in maintaining homeostasis of HSC in the normal and diseased BM microenvironment.…”

Section: Trained Innate Immunity In Hsc Transplantationmentioning

confidence: 99%

Trained Innate Immunity in Hematopoietic Stem Cell and Solid Organ Transplantation

Cunningham

Mills

2021

Transplantation

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Although significant progress has been made to improve short-term survival of transplant patients, long-term acceptance of allografts in solid organ and hematopoietic stem cell (HSC) transplantation is still a significant challenge. Current therapeutics for preventing or treating allograft rejection rely on potent immunosuppressive drugs that primarily target T cells of the adaptive immune response. Promising advances in transplant immunology have highlighted the importance of innate immune responses in allograft acceptance and rejection. Recent studies have demonstrated that innate immune cells are capable of mediating memory-like responses during inflammation, a term known as trained innate immunity. In this process, innate immune cells, such as macrophages and monocytes, undergo metabolic and epigenetic changes in response to a primary stimulus with a pathogen or their products that result in faster and more robust responses to a secondary stimulus. There is also some evidence to suggest that innate immune cells or their progenitors may be more anti-inflammatory after initial stimulation with appropriate agents, such as helminth products. Although this phenomenon has primarily been studied in the context of infection, there is emerging evidence to suggest that it could play a vital role in transplantation rejection and tolerance. Mechanisms of training innate immune cells and their progenitors in the bone marrow are therefore attractive targets for mediating long-term solid organ and HSC transplant tolerance. In this review, we highlight the potential role of proinflammatory and anti-inflammatory mechanisms of trained innate immunity in solid organ and HSC transplantation.

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“…Both interferon-gamma (IFN-γ) and tumor necrosis factor (TNF)-β are important cytotoxic factors that can promote brain microglial cells and macrophages to eliminate xenogenic cells ( 11 , 41 , 42 ). MHC-I has been reported to assist in immune recognition in reconstructing synapse connections ( 43 , 44 ), whereas MHC-II helps to clear mismatched xenogenic cells ( 38 , 45 ). Therefore, the responses of MHC-II-positive microglial cells at later stages better reflect the occurrence of heterologous cell rejection.…”

Section: Discussionmentioning

confidence: 99%

Immunological Responses to Transgene-Modified Neural Stem Cells After Transplantation

Wei

Sun

et al. 2021

Front. Immunol.

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Neural stem cell (NSC) therapy is a promising therapeutic strategy for stroke. Researchers have frequently carried out genetic modification or gene editing of stem cells to improve survival or therapeutic function. However, NSC transplantation carries the risk of immune rejection, and genetic modification or gene-editing might further increase this risk. For instance, recent studies have reported on manipulating the stem cell genome and transplantation via the insertion of an exogenous gene derived from magnetotactic bacteria. However, whether transgene-modified stem cells are capable of inducing immunological reactions has not been explored. Although NSCs rarely express the major histocompatibility complex (MHC), they can still cause some immunological issues. To investigate whether transgene-modified NSCs aggravate immunological responses, we detected the changes in peripheral immune organs and intracerebral astrocytes, glial cells, and MHC-I and MHC-II molecules after the injection of GFP-labeled or mms6-GFP-labeled NSCs in a rat model. Xenogeneic human embryonic kidney (HEK-293T) cells were grafted as a positive control group. Our results indicated that xenogeneic cell transplantation resulted in a strong peripheral splenic response, increased astrocytes, enhanced microglial responses, and upregulation of MHC-I and MHC-II expression on the third day of transplantation. But they decreased obviously except Iba-1 positive cells and MHC-II expression. When injection of both mms6-GFP-labeled NSCs and GFP-labeled NSCs also induced similar responses as HEK-293T cells on the third days, but MHC-I and MHC-II expression decreased 3 weeks after transplantation. In addition, mms6 transgene-modified NSCs did not produce peripheral splenic response responses as well as astrocytes, microglial cells, MHC-I and MHC-II positive cells responses when compared with non-modified NSCs. The present study provides preliminary evidence that transgenic modification does not aggravate immunological responses in NSC transplantation.

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MHC Class I Expression by Donor Hematopoietic Stem Cells Is Required to Prevent NK Cell Attack in Allogeneic, but Not Syngeneic Recipient Mice

Cited by 6 publications

References 16 publications

CD150high Bone Marrow Tregs Maintain Hematopoietic Stem Cell Quiescence and Immune Privilege via Adenosine

CD150high Bone Marrow Tregs Maintain Hematopoietic Stem Cell Quiescence and Immune Privilege via Adenosine

Trained Innate Immunity in Hematopoietic Stem Cell and Solid Organ Transplantation

Immunological Responses to Transgene-Modified Neural Stem Cells After Transplantation

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