Tolerance induction towards cardiac allografts under costimulation blockade is impaired in CCR7‐deficient animals but can be restored by adoptive transfer of syngeneic plasmacytoid dendritic cells

Liu, Xiaosun; Mishra, Pooja; Yu, Songfeng; Beckmann, Jan; Wendland, Meike; Kocks, Jessica R.; Seth, Sebastian; Hoffmann, Katharina; Hoffmann, Matthias; Kremmer, Elisabeth; Förster, Reinhold; Worbs, Tim

doi:10.1002/eji.201040877

Cited by 21 publications

(22 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Last, CCR7 is known to be involved in the localization of both DCs and T cells in the T-cell-rich zones of the LNs, indicating a role for CCR7 in T-cell homing and priming (Hopken et al 2004). Recently, Liu et al (2011) showed that a lack of CCR7 prevented tolerance induction in a cardiac murine model of transplantation. This impairment of tolerance was partially rescued by adoptive transfer of wild-type plasmacytoid DCs to the CCR7-deficient mice (Liu et al 2011).…”

Section: Chemokinesmentioning

confidence: 99%

See 1 more Smart Citation

Effector Mechanisms of Rejection

Moreau

Varey

Anegón

et al. 2013

Cold Spring Harbor Perspectives in Medicine

145

136

View full text Add to dashboard Cite

Section: Chemokinesmentioning

confidence: 99%

“…Recently, Liu et al (2011) showed that a lack of CCR7 prevented tolerance induction in a cardiac murine model of transplantation. This impairment of tolerance was partially rescued by adoptive transfer of wild-type plasmacytoid DCs to the CCR7-deficient mice (Liu et al 2011).…”

Section: Chemokinesmentioning

confidence: 99%

Effector Mechanisms of Rejection

Moreau

Varey

Anegón

et al. 2013

Cold Spring Harbor Perspectives in Medicine

145

136

View full text Add to dashboard Cite

“…These specialized vessels are lined abluminally with basement membrane stromal fibers. HEVs are luminally lined with blood endothelial cells (BECs) expressing the CD62L ligand peripheral node addressin (PNAd), which mediates the tethering and rolling of T cells (5,17). T cell arrest on the endothelium is mediated by CCR7 and CXCR4 recognition of CCL21 and CXCL12, respectively, and these chemokines decorate the luminal surface of the HEV.…”

Section: Introductionmentioning

confidence: 99%

Laminins affect T cell trafficking and allograft fate

Warren¹,

Iwami²,

Harris³

et al. 2014

J. Clin. Invest.

View full text Add to dashboard Cite

Lymph nodes (LNs) are integral sites for the generation of immune tolerance, migration of CD4 + T cells, and induction of Tregs. Despite the importance of LNs in regulation of inflammatory responses, the LN-specific factors that regulate T cell migration and the precise LN structural domains in which differentiation occurs remain undefined. Using intravital and fluorescent microscopy, we found that alloreactive T cells traffic distinctly into the tolerant LN and colocalize in exclusive regions with alloantigen-presenting cells, a process required for Treg induction. Extracellular matrix proteins, including those of the laminin family, formed regions within the LN that were permissive for colocalization of alloantigen-presenting cells, alloreactive T cells, and Tregs. We identified unique expression patterns of laminin proteins in high endothelial venule basement membranes and the cortical ridge that correlated with alloantigen-specific immunity or immune tolerance. The ratio of laminin α4 to laminin α5 was greater in domains within tolerant LNs, compared with immune LNs, and blocking laminin α4 function or inducing laminin α5 overexpression disrupted T cell and DC localization and transmigration through tolerant LNs. Furthermore, reducing α4 laminin circumvented tolerance induction and induced cardiac allograft inflammation and rejection in murine models. This work identifies laminins as potential targets for immune modulation.

show abstract

“…In general, the level at which administered DCs successfully reach their intended final destination is low. The chemokine receptor CCR7, which mediates migration of tolDCs to lymph nodes in vivo, is thought to be critical in this respect [20,21]. Moreover, the tolDCs should also be capable of migrating to the specific tissues where autoimmunity occurs.…”

mentioning

confidence: 99%

Fulfilling the dream: tolerogenic dendritic cells to treat multiple sclerosis

2012

View full text Add to dashboard Cite

Autoimmune diseases including multiple sclerosis (MS) are the result of an imbalanced immune tolerance network. Dendritic cells (DCs) are key players in both initiating immunity (immunogenic DCs) and regulating immune responses (tolerogenic DCs= IntroductionMultiple sclerosis (MS) is the prototype of a central nervous system (CNS) directed, antigen-driven, predominantly T-cell medi- Immunological tolerance induction, its maintenance by DCs and what goes wrong in MSThe major subtypes of human DCs are conventional myeloid (CD11c + ) DCs (mDCs) and type I interferon-secreting plasmacytoid (CD11c dim CD123 + ) DCs (pDCs). Depending on the antigen presented and the activation status of the DCs, both subsets can either exhibit immunogenic or tolerogenic features [9,10]. Immature DCs are located in the peripheral tissues where they constantly encounter/sample antigens. While TLR ligands and pro-inflammatory cytokines induce maturation into immunogenic DCs that migrate to secondary lymphoid organs where they prime naïve T cells, anti-inflammatory cytokines including IL-10 and TGF-β induce DCs with a more tolerogenic phenotype (tolDCs) [10]. The term tolDCs summarizes a heterogeneous group of different DC subsets (mDCs and pDCs) located in various tissues where they use different mechanisms to induce and maintain both central and peripheral tolerance. In the thymus, DCs eliminate autoreactive T cells by clonal deletion of high-affinity thymocytes or diversion into Treg cells [11]. Despite these central tolerance mechanisms, some low avidity autoreactive T cells escape into the periphery, where peripheral tolerance mechanisms are required to prevent spontaneous autoimmunity. Multiple peripheral tolerance mechanisms have been identified for myelin-specific T cells, most importantly Treg cells and tolerogenic DCs [5,12]. TolDCs keep autoreactive T cells under control by inducing anergy, apoptosis, phenotypic skewing, and/or Treg cells [13][14][15].In MS, both immunogenic and tolerogenic features of different DC subsets are disrupted [7,12]. Elevated numbers of mature mDCs have been found in the peripheral blood of MS patients, and the occurrence of both mDCs and pDCs in the CSF of MS patients suggests their active participation in disease pathogenesis [12]. Furthermore, alterations in phenotype and/or function of different DC subsets have been observed in MS [7,12]. pDCs for example show an imbalance in the ratio between tolerogenic and immunogenic subtypes generating a propensity to generate proinflammatory Th17 cell responses in MS [16]. The "dysfunctional state" of certain DC subsets in MS could be linked to the observation of dysfunctional Treg-cell responses in MS [5]. Therefore, therapies targeting DCs for MS aim to either diminish their immunogenic potential or enhance their tolerogenic features [7]. Chances and pitfalls of the therapeutic use of tolDCsSo far, most of our knowledge in using tolDCs to treat autoimmunity is derived from extensive work in animal models including experimental autoimmune encephalitis (EA...

show abstract

Tolerance induction towards cardiac allografts under costimulation blockade is impaired in CCR7‐deficient animals but can be restored by adoptive transfer of syngeneic plasmacytoid dendritic cells

Cited by 21 publications

References 41 publications

Effector Mechanisms of Rejection

Effector Mechanisms of Rejection

Laminins affect T cell trafficking and allograft fate

Fulfilling the dream: tolerogenic dendritic cells to treat multiple sclerosis

Contact Info

Product

Resources

About