Specific immunosuppressive role of nanodrugs targeting calcineurin in innate myeloid cells

Colombo, Miriam; Marongiu, Laura; Mingozzi, Francesca; Marzi, Roberta; Cigni, Clara; Facchini, Fabio A.; Rotem, Rany; Valache, Mihai; Stucchi, Giulia; Rocca, Giuseppe La; Gornati, Laura; Rizzuto, Maria Antonietta; Salvioni, Lucia; Zanoni, Ivan; Gori, Alessandro; Prosperi, Davide; Granucci, Francesca

doi:10.1016/j.isci.2022.105042

Cited by 9 publications

(6 citation statements)

References 53 publications

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“…Indeed these drugs which have not been designed to target innate immunity, include corticosteroids, calcineurin inhibitors, and/or mycophenolate, and their effects on mononuclear cells are not known and could be investigated with this platform [ 29 ]. Indeed a recent publication demonstrated in mice that targeting a calcineurin inhibitor to myeloid phagocytes induced better protection against skin graft rejection than the conventional administration that aims at suppressing lymphocytes [ 30 ]. New therapeutic avenues such as administration of mesenchymal stem cells [ 31 ] or photopheresis [ 32 ] could be similarly tested.…”

Section: Discussionmentioning

confidence: 99%

A cross-circulatory platform for monitoring innate allo-responses in lung grafts

et al. 2023

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Lung transplantation is the only curative option for end-stage chronic respiratory diseases. However the survival rate is only about 50% at 5 years. Although experimental evidences have shown that innate allo-responses impact on the clinical outcome, the knowledge of the involved mechanisms involved is limited. We established a cross-circulatory platform to monitor the early recruitment and activation of immune cells in an extracorporeal donor lung by coupling blood perfusion to cell mapping with a fluorescent marker in the pig, a commonly-used species for lung transplantation. The perfusing pig cells were easily detectable in lung cell suspensions, in broncho-alveolar lavages and in different areas of lung sections, indicating infiltration of the organ. Myeloid cells (granulocytes and monocytic cells) were the dominant recruited subsets. Between 6 and 10 h of perfusion, recruited monocytic cells presented a strong upregulation of MHC class II and CD80/86 expression, whereas alveolar macrophages and donor monocytic cells showed no significant modulation of expression. This cross-circulation model allowed us to monitor the initial encounter between perfusing cells and the lung graft, in an easy, rapid, and controllable manner, to generate robust information on innate response and test targeted therapies for improvement of lung transplantation outcome.

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Section: Discussionmentioning

confidence: 99%

A cross-circulatory platform for monitoring innate allo-responses in lung grafts

et al. 2023

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“…For instance, the pretreatment of a donor’s lungs with CS before lung procurement may improve the anti-inflammatory effect on the innate allo-response, an option that we are currently evaluating. In addition, combination with other drugs or biologicals (rapamycine, calcineurin inhibitors, GM-CSF) that is variable between transplantation centers, and the testing of other types of corticosteroids should be further explored using our cross-circulation platform for their compared efficacy versus the baseline of the current methylprednisolone treatment ( 3 ).…”

Section: Discussionmentioning

confidence: 99%

“…It has recently been proposed that the control of the innate immune responses during LT, through targeting myeloid cells, could result in tolerance induction and prolonged graft survival ( 2 , 3 ). The innate immune responses in LT are induced by the ischemia-reperfusion process that inevitably occurs upon reoxygenation of the explanted lung and is responsible for a complex sterile inflammatory cascade driven by polymorphonuclear cells (PMNs), resident alveolar macrophages (AMs) and monocytic cell subsets of hematopoietic origin ( 4 ).…”

Section: Introductionmentioning

confidence: 99%

Differential early response of monocyte/macrophage subsets to intra-operative corticosteroid administration in lung transplantation

Glorion,

Pascale,

Huriet

et al. 2023

Front. Immunol.

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IntroductionLung transplantation often results in primary and/or chronic dysfunctions that are related to early perioperative innate allo-responses where myeloid subsets play a major role. Corticosteroids are administered upon surgery as a standard-of-care but their action on the different myeloid cell subsets in that context is not known.MethodsTo address this issue, we used a cross-circulatory platform perfusing an extracorporeal lung coupled to cell mapping in the pig model, that enabled us to study the recruited cells in the allogeneic lung over 10 hours.ResultsMyeloid cells, i.e. granulocytes and monocytic cells including classical CD14pos and non-classical/intermediate CD16pos cells, were the dominantly recruited subsets, with the latter upregulating the membrane expression of MHC class II and CD80/86 molecules. Whereas corticosteroids did not reduce the different cell subset recruitment, they potently dampened the MHC class II and CD80/86 expression on monocytic cells and not on alveolar macrophages. Besides, corticosteroids induced a temporary and partial anti-inflammatory gene profile depending on cytokines and monocyte/macrophage subsets.DiscussionThis work documents the baseline effects of the standard-of-care corticosteroid treatment for early innate allo-responses. These insights will enable further optimization and improvement of lung transplantation outcomes.

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“…Colombo et al screened for VIVIT peptides with a high affinity for calcium-regulated neurophosphatase (CN), using them to inhibit the interaction between CN and NFAT to and block the CN/NFAT pathway. Delivery of VIVIT peptides using nanoparticles targeting DCs not only prevents graft rejection during treatment but also induces long-term skin graft tolerance after the end of treatment compared to the immunosuppressant FK-506 in a skin graft model ( Colombo et al, 2022 ).…”

Section: Nanodrug Delivery Systems Targeting Dcs To Induce Immune Tol...mentioning

confidence: 99%

“…The NFAT signaling pathway in DCs is responsible for inducing effective T cell activation and graft rejection. Blocking the NFAT signaling pathway on DCs can inhibit the proliferation of antigen-specific T cells and plays a role in inducing graft tolerance (Otsuka et al, 2021;Colombo et al, 2022). Colombo et al screened for VIVIT peptides with a high affinity for calcium-regulated neurophosphatase (CN), using them to inhibit the interaction between CN and NFAT to and block the CN/NFAT pathway.…”

Section: Induction Of Autoantigen-based Immune Tolerance By DC Target...mentioning

confidence: 99%

Advances in dendritic cell targeting nano-delivery systems for induction of immune tolerance

Lin,

Wang,

Yang

et al. 2023

Front. Bioeng. Biotechnol.

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Dendritic cells (DCs) are the major specialized antigen-presenting cells (APCs), play a key role in initiating the body’s immune response, maintain the balance of immunity. DCs can also induce immune tolerance by rendering effector T cells absent and anergy, and promoting the expansion of regulatory T cells. Induction of tolerogenic DCs has been proved to be a promising strategy for the treatment of autoimmune diseases, organ transplantation, and allergic diseases by various laboratory researches and clinical trials. The development of nano-delivery systems has led to advances in situ modulation of the tolerance phenotype of DCs. By changing the material composition, particle size, zeta-potential, and surface modification of nanoparticles, nanoparticles can be used for the therapeutic payloads targeted delivery to DCs, endowing them with great potential in the induction of immune tolerance. This paper reviews how nano-delivery systems can be modulated for targeted delivery to DCs and induce immune tolerance and reviews their potential in the treatment of autoimmune diseases, organ transplantation, and allergic diseases.

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Specific immunosuppressive role of nanodrugs targeting calcineurin in innate myeloid cells

Cited by 9 publications

References 53 publications

A cross-circulatory platform for monitoring innate allo-responses in lung grafts

A cross-circulatory platform for monitoring innate allo-responses in lung grafts

Differential early response of monocyte/macrophage subsets to intra-operative corticosteroid administration in lung transplantation

Advances in dendritic cell targeting nano-delivery systems for induction of immune tolerance

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