Duality at the gate: Skin dendritic cells as mediators of vaccine immunity and tolerance

Nirschl, Christopher J.; Anandasabapathy, Niroshana

doi:10.1080/21645515.2015.1066050

Cited by 10 publications

(12 citation statements)

References 144 publications

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“…DCs imprint naïve responses to direct the differentiation of CD4 helper T cells into T H 1, T H 2, T H 17, Tfh, Tr1, and Treg (9–14). Multiple specialized subtypes of DCs that have been identified can be distinguished by surface markers, which have recently been correlated to their unique transcriptome based programs across mice and humans (15–21). …”

Section: Introductionmentioning

confidence: 99%

Near-Infrared 1064 nm Laser Modulates Migratory Dendritic Cells To Augment the Immune Response to Intradermal Influenza Vaccine

Morse

Kimizuka

Chan

et al. 2017

The Journal of Immunology

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Brief exposure of skin to near-infrared (NIR) laser light has been shown to augment the immune response to intradermal vaccination and thus act as an immunologic adjuvant. Although evidence indicates that the NIR laser adjuvant has capacity to activate innate subsets including dendritic cells (DCs) in skin as conventional adjuvants do, the precise immunological mechanism by which the NIR laser adjuvant acts is largely unknown. Here we sought to identify the cellular target of the NIR laser adjuvant by using an established mouse model of intradermal influenza vaccination and examining the alteration of responses resulting from genetic ablation of specific DC populations. We found that a continuous wave (CW) NIR laser adjuvant broadly modulates migratory DC populations, specifically increasing and activating the Lang+ and CD11b−Lang− subsets in skin, and that the antibody responses augmented by the CW NIR laser are dependent on DC subsets expressing CCR2 and Langerin. In comparison, a pulsed wave (PW) NIR laser adjuvant showed limited effects on the migratory DC subsets. Our vaccination study demonstrated that the efficacy of CW NIR laser is significantly better than that of PW laser, indicating that the CW NIR laser offers a desirable immunostimulatory microenvironment for migratory DCs. These results demonstrate the unique ability of the NIR laser adjuvant to selectively target specific migratory DC populations in skin depending on its parameters, and highlight the importance of optimization of laser parameters for desirable immune protection induced by a NIR laser-adjuvanted vaccine.

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Section: Introductionmentioning

confidence: 99%

Near-Infrared 1064 nm Laser Modulates Migratory Dendritic Cells To Augment the Immune Response to Intradermal Influenza Vaccine

Morse

Kimizuka

Chan

et al. 2017

The Journal of Immunology

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“…It remains unknown if and how these cells have evolved conserved mechanisms of maintaining self tolerance. Homeostatic maturation linked to migration from tissues and leading to tolerance [11, 12] has been distinguished from danger signal based licensing leading to adaptive immunity [13]…”

Section: How Are Tolerance and Immunity Simultaneous Achieved?mentioning

confidence: 99%

“…In the steady state 5-7 % have been estimated to navigate to nearest lymph node for antigen presentation to T cells [12] (while under local inflammatory conditions their migratory rate is significantly increased [6, 8]. Transendothelial migration of pre-DCs to non-lymphoid tissues such as skin is mediated by receptor-ligand interactions, such as CCR4-CCL22/CCL17, CCR6-CCL20, CCR2-CCL2, CCR5-CCL5, and CXCR3-CXCL9/CXCL10/CXCL11.…”

Section: Overview Of DC Subsets and Functional Specializationmentioning

confidence: 99%

The origin of DCs and capacity for immunologic tolerance in central and peripheral tissues

Devi

Anandasabapathy

2016

Semin Immunopathol

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Dendritic cells (DCs) are specialized immune sentinels that play key role in maintaining immune homeostasis by efficiently regulating the delicate balance between protective immunity and tolerance to self. Although DCs respond to maturation signals present in the surrounding milieu multiple layers of suppression also co-exist that reduce the infringement of tolerance against self-antigens. These tolerance inducing properties of DCs are governed by their origin and a range of other factors including distribution, cytokines, growth factors, and transcriptional programing, that collectively impart suppressive functions to these cells. DCs directing tolerance secrete anti-inflammatory cytokines and induce naïve T cells or B cells to differentiate into regulatory T cells (Tregs) or B cells. In this review, we provide a detailed outlook on the molecular mechanisms that induce functional specialization to govern central or peripheral tolerance. The tolerance-inducing nature of DCs can be exploited to overcome autoimmunity and rejection in graft transplantation.

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“…This new and safe strategy has been logically combined with skin vaccination to maximize the efficacy of vaccines and induce protection. The skin is enriched with professional antigen‐presenting dendritic cells (DCs) and has been considered to be an ideal vaccination site to initiate adaptative immune responses and protection when DCs are provided with a proper cue . Skin‐based vaccination to target antigen‐presenting cells (APCs) has been consistently shown to be superior to the conventional intramuscular route and offer dose sparing .…”

Section: Introductionmentioning

confidence: 99%

“…The skin is enriched with professional antigen-presenting dendritic cells (DCs) and has been considered to be an ideal vaccination site to initiate adaptative immune responses and protection when DCs are provided with a proper cue. 13 Skin-based vaccination to target antigen-presenting cells (APCs) has been consistently shown to be superior to the conventional intramuscular route [14][15][16] and offer dose sparing. [17][18][19] In response to these advantages, various technologies are now in use or under development for skin delivery of vaccines.…”

Section: Introductionmentioning

confidence: 99%

Laser adjuvant for vaccination

Kashiwagi

2020

FASEB j.

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The use of an immunologic adjuvant to augment the immune response is essential for modern vaccines which are relatively ineffective on their own. In the past decade, researchers have been consistently reporting that skin treatment with a physical parameter, namely laser light, augments the immune response to vaccine and functions as an immunologic adjuvant. This “laser adjuvant” has numerous advantages over the conventional chemical or biological agents; it is free from cold chain storage, hypodermic needles, biohazardous sharp waste, irreversible formulation with vaccine antigen, undesirable biodistribution in vital organs, or unknown long‐term toxicity. Since vaccine formulations are given to healthy populations, these characteristics render the “laser adjuvant” significant advantages for clinical use and open a new developmental path for a safe and effective vaccine. In addition, laser technology has been used in the clinic for more than three decades and is therefore technically matured and has been proved to be safe. Currently, four classes of laser adjuvant have been reported; ultrashort pulsed, non‐pulsed, non‐ablative fractional, and ablative fractional lasers. Since each class of the laser adjuvant shows a distinct mechanism of action, a proper choice is necessary to craft an effective vaccine formulation toward a desired clinical benefit for a clinical vaccine to maximize protection. In addition, data also suggest that further improvement in the efficacy is possible when a laser adjuvant is combined with chemical or biological adjuvant(s). To realize these goals, further efforts to uncover the molecular mechanisms of action of the laser adjuvants is warranted. This review provides a summary and comments of the recent updates in the laser adjuvant technology.

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Duality at the gate: Skin dendritic cells as mediators of vaccine immunity and tolerance

Cited by 10 publications

References 144 publications

Near-Infrared 1064 nm Laser Modulates Migratory Dendritic Cells To Augment the Immune Response to Intradermal Influenza Vaccine

Near-Infrared 1064 nm Laser Modulates Migratory Dendritic Cells To Augment the Immune Response to Intradermal Influenza Vaccine

The origin of DCs and capacity for immunologic tolerance in central and peripheral tissues

Laser adjuvant for vaccination

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