Materials that harness and modulate the immune system

Lewis, Jamal S.; Roy, Krishnendu; Keselowsky, Benjamin G.

doi:10.1557/mrs.2013.310

Cited by 46 publications

(40 citation statements)

References 82 publications

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“…Peptide-MHC-I complexes interact with CD8+ T cells. On the other hand, CD4+ T cells form immunological synapses via interaction with peptide-loaded MHC-II molecules, which display exogenously-acquired antigen following endosomal degradation and cathepsin S-assisted loading [41]. An alternative pathway of antigen presentation exists, where subsets of DCs efficiently present exogenously-derived antigen fragments onto MHC-I molecules.…”

Section: Dendritic Cell Antigen Presentationmentioning

confidence: 99%

Dendritic cells in the host response to implanted materials

Keselowsky

Lewis

2017

Seminars in Immunology

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The role of dendritic cells (DCs) and their targeted manipulation in the body’s response to implanted materials is an important and developing area of investigation, and a large component of the emerging field of biomaterials-based immune engineering. The key position of DCs in the immune system, serving to bridge innate and adaptive immunity, is facilitated by rich diversity in type and function and places DCs as a critical mediator to biomaterials of both synthetic and natural origins. This review presents current views regarding DC biology and summarizes recent findings in DC responses to implanted biomaterials. Based on these findings, there is promise that the directed programming of application-specific DC responses to biomaterials can become a reality, enabling and enhancing applications almost as diverse as the larger field of biomaterials itself.

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Section: Dendritic Cell Antigen Presentationmentioning

confidence: 99%

Dendritic cells in the host response to implanted materials

Keselowsky

Lewis

2017

Seminars in Immunology

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“…7,11 Dendritic cells are the most efficient antigen presenting cells (APCs), capable of orchestrating lymphocyte function and directing the immune response toward either immunity or tolerance. 12–15 Exploiting this potential, DCs have been manipulated both ex vivo and in vivo through controlled release schemes 16 to treat a number of diseases such as cancer, 17–19 infection 20,21 and autoimmunity 22 such as type-1 diabetes. 23–25 A next step in DC modulation involves simultaneously providing combinations of multiple different TLR ligands, which is capable of inducing synergistic increases in antigen-specific immune responses.…”

Section: Introductionmentioning

confidence: 99%

A cell-based microarray to investigate combinatorial effects of microparticle-encapsulated adjuvants on dendritic cell activation

et al. 2016

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Experimental vaccine adjuvants are being designed to target specific toll-like receptors (TLRs) alone or in combination, expressed by antigen presenting cells, notably dendritic cells (DCs). There is a need for high-content screening (HCS) platforms to explore how DC activation is affected by adjuvant combinations. Presented is a cell-based microarray approach, “immunoarray”, exposing DCs to a large number of adjuvant combinations. Microparticles encapsulating TLR ligands are printed onto arrays in a range of doses for each ligand, in all possible dose combinations. Dendritic cells are then co-localized with physisorbed microparticles on the immunoarray, adherent to isolated islands surrounded by a non-fouling background, and DC activation is quantified. Delivery of individual TLR ligands was capable of eliciting high levels of specific DC activation markers. For example, either TLR9 ligand, CpG, or TLR3 ligand, poly I:C, was capable of inducing among the highest 10% expression levels of CD86. In contrast, MHC-II expression in response to TLR4 agonist MPLA was among the highest, whereas either MPLA or poly I:C, was capable of producing among the highest levels of CCR7 expression, as well as inflammatory cytokine IL-12. However, in order to produce robust responses across all activation markers, adjuvant combinations were required, and combinations were more represented among the high responders. The immunoarray also enables investigation of interactions between adjuvants, and each TLR ligand suggested antagonism to other ligands, for various markers. Altogether, this work demonstrates feasibility of the immunoarray platform to screen microparticle-encapsulated adjuvant combinations for the development of improved and personalized vaccines.

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“…Active targeting of particulates may improve cargo delivery, reduce harmful off-target effects, and initiate immune receptor-signaling pathways. 2 Particulate active targeting can be accomplished by surface absorption or ligation of ligands with high affinity for specific molecules found on the surface of immune cells. In the context of tolerogenic applications, it is vital that engagement of these surface receptors does not stimulate inflammatory pathways.…”

Section: Particulate Engineering For Tolerogenic Outcomesmentioning

confidence: 99%

An introduction to biomaterial-based strategies for curbing autoimmunity

Lewis

Allen

2016

Exp Biol Med (Maywood)

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Recently, scientists have made significant progress in the development of immunotherapeutics that correct aberrant, autoimmune responses. Yet, concerns about the safety, efficacy, and wide scale applicability continue to hinder use of contemporary, immunology-based strategies. There is a clear need for therapies that finely control molecular and cellular elements of the immune system. Biomaterial engineers have taken up this challenge to develop therapeutics with selective spatial and temporal control of immune cells. In this review, we introduce the immunology of autoimmune disorders, survey the current therapeutic strategies for autoimmune diseases, and highlight the ongoing research efforts to engineer the immune system using biomaterials, for positive therapeutic outcomes in treatment of autoimmune disorders.

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Materials that harness and modulate the immune system

Cited by 46 publications

References 82 publications

Dendritic cells in the host response to implanted materials

Dendritic cells in the host response to implanted materials

A cell-based microarray to investigate combinatorial effects of microparticle-encapsulated adjuvants on dendritic cell activation

An introduction to biomaterial-based strategies for curbing autoimmunity

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