Proinflammatory human 6-sulfo LacNAc-positive dendritic cells accumulate in intestinal acute graft-versus-host disease

Sommer, Ulrich; Larsson, Brit; Tuve, Sebastian; Wehner, Rebekka; Zimmermann, Nick; Kramer, Michael; Kloβ, Anja; Günther, Claudia; Babatz, Jana; Schmelz, Renate; Brückner, Stefan; Schetelig, Johannes; Bornhäuser, Martin; Schäkel, Knut; Bachmann, Michael; Aust, Daniela E.; Baretton, Gustavo; Schmitz, Marc

doi:10.3324/haematol.2013.101071

Cited by 10 publications

(12 citation statements)

References 18 publications

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“…Contrary to our expectations, we could observe occasional slanDCs only in biopsy samples obtained from intestinal aGVHD, being undetectable in all the remaining tissue sections examined. It is worthy of note that the presence of slanDCs in intestinal biopsy specimens from aGVHD patients has been confirmed very recently in a series of colorectal aGVHD samples by immunohistochemistry (IHC) . In our opinion, the selective presence of slanDCs in intestinal aGVHD specimens could be related, similar to what has been observed in Crohn's disease , to a specific inflammatory pattern of aGVHD in the bowel.…”

Section: Discussionsupporting

confidence: 70%

“…In our opinion, the selective presence of slanDCs in intestinal aGVHD specimens could be related, similar to what has been observed in Crohn's disease , to a specific inflammatory pattern of aGVHD in the bowel. In this latter tissue, slanDCs could also play an immunopathogenetic role, given their local expression of TNF‐α and IL‐23 and co‐localization with T cells .…”

Section: Discussionmentioning

confidence: 99%

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Rapid reconstitution of functionally active 6-sulfoLacNAc+ dendritic cells (slanDCs) of donor origin following allogeneic haematopoietic stem cell transplant

Mimiola

Marini

Perbellini

et al. 2014

Clinical and Experimental Immunology

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SummaryThe role of dendritic cells (DCs) and macrophages in allogeneic haematopoietic stem cell transplant (HSCT) is critical in determining the extent of graft-versus-host response. The goal of this study was to analyse slanDCs, a subset of human proinflammatory DCs, in haematopoietic stem cell (HSC) sources, as well as to evaluate their 1-year kinetics of reconstitution, origin and functional capacities in peripheral blood (PB) and bone marrow (BM) of patients who have undergone HSCT, and their presence in graft-versus-host disease (GVHD) tissue specimens. slanDCs were also compared to myeloid (m)DCs, plasmacytoid (p)DCs and monocytes in HSC sources and in patients' PB and BM throughout reconstitution. slanDCs accounted for all HSC sources. In patients' PB and BM, slanDCs were identified from day +21, showing median frequencies comparable to healthy donors, donor origin and kinetics of recovery similar to mDCs, pDCs, and monocytes. Under cyclosporin treatment, slanDCs displayed a normal pattern of maturation, and maintained an efficient chemotactic activity and capacity of releasing tumour necrosis factor (TNF)-α upon lipopolysaccharide (LPS) stimulation. None the less, they were almost undetectable in GVHD tissue specimens, being present only in intestinal acute GVHD samples. slanDCs reconstitute early, being donor-derived and functionally competent. The absence of slanDCs from most of the GVHD-targeted tissue specimens seems to rule out the direct participation of these cells in the majority of the local reactions characterizing GVHD.

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Section: Discussionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Rapid reconstitution of functionally active 6-sulfoLacNAc+ dendritic cells (slanDCs) of donor origin following allogeneic haematopoietic stem cell transplant

Mimiola

Marini

Perbellini

et al. 2014

Clinical and Experimental Immunology

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“…Interessanterweise liegt in metastatischen Lymphknoten eine Kolokalisation von slanDCs mit NK-Zellen und neutrophilen Granulozyten vor. von slanDCs sind entzündliche Tonsillen [ 31,36 ] , das Ileum von Patienten mit Morbus Crohn [ 36 ] , die entzündete Synovia der rheumatoiden Arthritis [ 11 ] sowie die intestinale Graft-versus-Host-Disease [ 37 ] .…”

Section: Tumorerkrankungenunclassified

The role of human 6‐sulfo LacNAc dendritic cells (slanDCs) in autoimmunity and tumor diseases

Döbel

Schäkel

2014

J Deutsche Derma Gesell

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SummaryDendritic cells play a central role in the regulation of immunological reactivity. The existence of functionally specialized populations of dendritic cells in the skin is a consequence of qualitatively different attacks on our organism. slanDCs are human inflammatory dendritic cells that are characterized by the specific expression of the carbohydrate 6-sulfo LacNAc (slan). After phenotypic maturation, slanDCs are capable of producing very high amounts of proinflammatory mediators such as IL-12, TNF-α, IL-1β and IL-23. Recent data describe a potential role of slanDCs in a number of different diseases like psoriasis, lupus erythematosus, and tumors, thus opening up new areas of research on their respective pathogenesis. Furthermore, a slanDC-specific targeting system has been developed as a basis for direct therapeutic manipulation. Future challenges of slanDC research include deepening our understanding of the significance of slanDCs in the regulation of adaptive and innate immune responses, as well as translating this knowledge into therapeutic options.

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“…For example, in the HSCT treatment, donor‐derived CD4+ helper T cells and CD8+ cytotoxic T lymphocytes (CTLs) produce various inflammatory cytokines to lyse targeted cells in recipients, thus leading to GVHD. As functional antigen‐presenting cells (APCs), DCs facilitate this process by inducing and augmenting CD4+ helper T cells and CD8+ CTLs, whose number can increase rapidly in the lymph nodes during the early stage of transplantation and within 20 hours of continuous interaction with DCs . Furthermore, a recent study utilizing a syngeneic C57BL/6(B6) mouse stem cell transplantation model showed that due to the absence of functional APCs, certain cells derived from iPSCs survived without rejection when transplanted under the kidney capsule.…”

Section: Bidirectional Regulatory Mechanisms Of Dcs In Stem Cell Tranmentioning

confidence: 99%

“…As functional antigen-presenting cells (APCs), DCs facilitate this process by inducing and augmenting CD4+ helper T cells and CD8+ CTLs, whose number can increase rapidly in the lymph nodes during the early stage of transplantation and within 20 hours of continuous interaction with DCs. 14,15 Furthermore, a recent study utilizing a syngeneic C57BL/6(B6) mouse stem cell transplantation model showed that due to the absence of functional APCs, certain cells derived from iPSCs survived without rejection when transplanted under the kidney capsule. However, these cells co-transplanted with mature B6 DCs under the kidney capsule led to immune rejection.…”

Section: Bidirectional Regulatory Mechanisms Of Dcs In Stem Cell Trmentioning

confidence: 99%

Immune roles of dendritic cells in stem cell transplantation

Zhang

Liao

Liu

et al. 2017

Clinical Transplantation

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Dendritic cells (DCs) are professional antigen-presenting cells and initial stimulators for immune response. DCs can shape their functions based on their immune states, which are crucial for the balance of immunity and tolerance to preserve homeostasis. In the immune response involved in stem cell transplantation, DCs also play important roles in inducing immune tolerance and antitumor immunity. After the rapid development of stem cell transplantation technology in recent years, the risks of graft rejection, tumor recurrence, and tumorigenicity are still present after stem cell transplantation. It is important to understand the mechanisms of DC-mediated immune tolerance and stimulation during stem cell transplantation. In this review, we will summarize and analyze the regulatory mechanisms of DCs in stem cell transplantation and their application in clinical settings. It may help to promote the innovation in basic theories and therapeutic approaches of stem cell transplantation.

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Proinflammatory human 6-sulfo LacNAc-positive dendritic cells accumulate in intestinal acute graft-versus-host disease

Abstract: LETTERS TO THE EDITOR © F e r r a t a S t o r t i F o u n d a t i o n

Cited by 10 publications

References 18 publications

Rapid reconstitution of functionally active 6-sulfoLacNAc+ dendritic cells (slanDCs) of donor origin following allogeneic haematopoietic stem cell transplant

Rapid reconstitution of functionally active 6-sulfoLacNAc+ dendritic cells (slanDCs) of donor origin following allogeneic haematopoietic stem cell transplant

The role of human 6‐sulfo LacNAc dendritic cells (slanDCs) in autoimmunity and tumor diseases

Immune roles of dendritic cells in stem cell transplantation

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