Lymph node stromal cells acquire peptide–MHCII complexes from dendritic cells and induce antigen-specific CD4+ T cell tolerance

Dubrot, Juan; Durães, Fernanda V.; Potin, Lambert; Capotosti, Francesca; Brighouse, Dale; Suter, Tobias; LeibundGut‐Landmann, Salomé; Garbi, Natalio; Reith, Walter; Swartz, Melody A.; Hugues, Stéphanie

doi:10.1084/jem.20132000

Cited by 208 publications

(232 citation statements)

References 47 publications

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“…In order to tightly control the microenvironment of LN, FRCs carry the potential to have both proinflammatory and regulatory functions (23,67). The initiation of immunoregulatory processes mediated by FRCs within the KLN likely promotes organ healing by suppressing inflammatory responses (68)(69)(70)(71). Because chronic depletion of FRCs with DT is challenging due to the high toxicity rate of long-term use, we sought to block the LTβr pathway to assess whether this alteration interferes with the healing phase of renal IRI.…”

Section: Discussionmentioning

confidence: 99%

Repetitive ischemic injuries to the kidneys result in lymph node fibrosis and impaired healing

Maarouf¹,

Uehara²,

Kasinath³

et al. 2018

JCI Insight

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Section: Discussionmentioning

confidence: 99%

Repetitive ischemic injuries to the kidneys result in lymph node fibrosis and impaired healing

Maarouf¹,

Uehara²,

Kasinath³

et al. 2018

JCI Insight

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“…Acquisition of MHC-I by NK cells from tumor cells leads to a reduced NK cytotoxic function (41). Acquisition of MHC-II from DCs via trogocytosis has been shown in CD4 T cells, NK cells, DCs, macrophages, and lymph node stromal cells (28,(42)(43)(44)(45). MHC-II-dressed recipient cells either stimulate or suppress T cells, perhaps depending on the expression and acquisition of costimulatory molecules (28).…”

Section: Cd11cmentioning

confidence: 99%

Trogocytosis of peptide–MHC class II complexes from dendritic cells confers antigen-presenting ability on basophils

Miyake

Shiozawa

Nagao

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

116

101

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Th2 immunity plays important roles in both protective and allergic responses. Nevertheless, the nature of antigen-presenting cells responsible for Th2 cell differentiation remains ill-defined compared with the nature of the cells responsible for Th1 and Th17 cell differentiation. Basophils have attracted attention as a producer of Th2-inducing cytokine IL-4, whereas their MHC class II (MHC-II) expression and function as antigen-presenting cells are matters of considerable controversy. Here we revisited the MHC-II expression on basophils and explored its functional relevance in Th2 cell differentiation. Basophils generated in vitro from bone marrow cells in culture with IL-3 plus GM-CSF displayed MHC-II on the cell surface, whereas those generated in culture with IL-3 alone did not. Of note, these MHC-II–expressing basophils showed little or no transcription of the corresponding MHC-II gene. The GM-CSF addition to culture expanded dendritic cells (DCs) other than basophils. Coculture of basophils and DCs revealed that basophils acquired peptide–MHC-II complexes from DCs via cell contact-dependent trogocytosis. The acquired complexes, together with CD86, enabled basophils to stimulate peptide-specific T cells, leading to their proliferation and IL-4 production, indicating that basophils can function as antigen-presenting cells for Th2 cell differentiation. Transfer of MHC-II from DCs to basophils was also detected in draining lymph nodes of mice with atopic dermatitis-like skin inflammation. Thus, the present study defined the mechanism by which basophils display MHC-II on the cell surface and appears to reconcile some discrepancies observed in previous studies.

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“…However, in the context of allo-HCT, FRCs and other fibroblastic stromal cells were shown to drive GVHD through presentation of Delta-like Notch ligands within the first 48 h after transplantation (41), suggesting that these cells can be proinflammatory. FRCs were also shown to display peptide-loaded MHC class II from exosomes released from cDCs, although in this context it was tolerogenic (42). One intriguing possibility is that, prior to their elimination by myeloablative conditioning, recipient hematopoietic APCs may transfer intact MHC molecules to non-hematopoietic cells such as FRCs for presentation to alloreactive T cells.…”

Section: Sites Of T Cell Priming In Graft-versus-host Diseasementioning

confidence: 99%

New Insights into Graft-Versus-Host Disease and Graft Rejection

Perkey

Maillard

2018

Annu. Rev. Pathol. Mech. Dis.

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Allogeneic transplantation of foreign organs or tissues has lifesaving potential, but can lead to serious complications. After solid organ transplantation, immune-mediated rejection mandates the use of prolonged global immunosuppression and limits the life span of transplanted allografts. After bone marrow transplantation, donor-derived immune cells can trigger life-threatening graft-versus-host disease. T cells are central mediators of alloimmune complications and the target of most existing therapeutic interventions. We review recent progress in identifying multiple cell types in addition to T cells and new molecular pathways that regulate pathogenic alloreactivity. Key discoveries include the cellular subsets that function as potential sources of alloantigens, the cross talk of innate lymphoid cells with damaged epithelia and with the recipient microbiome, the impact of the alarmin interleukin-33 on alloreactivity, and the role of Notch ligands expressed by fibroblastic stromal cells in alloimmunity. While refining our understanding of transplantation immunobiology, these findings identify new therapeutic targets and new areas of investigation.

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Lymph node stromal cells acquire peptide–MHCII complexes from dendritic cells and induce antigen-specific CD4+ T cell tolerance

Abstract: LNSCs present peptide–MHCII complexes acquired from DCs to CD4+ T cells and induce T cell dysfunction by preventing their proliferation and survival.

Cited by 208 publications

References 47 publications

Repetitive ischemic injuries to the kidneys result in lymph node fibrosis and impaired healing

Repetitive ischemic injuries to the kidneys result in lymph node fibrosis and impaired healing

Trogocytosis of peptide–MHC class II complexes from dendritic cells confers antigen-presenting ability on basophils

New Insights into Graft-Versus-Host Disease and Graft Rejection

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