Interleukin-32 promotes detachment and activation of human Langerhans cells in a human skin explant model

Gonnet, Jessica; Perrin, Hélène; Hutton, Andrew J.; Boccara, David; Bonduelle, Olivia; Mimoun, Maurice; Atlan, Michaël; Soria, Angèle; Combadière, Béhazine

doi:10.1111/bjd.16721

Cited by 7 publications

(7 citation statements)

References 38 publications

(88 reference statements)

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“…IL-6 production by DCs enhances CD8 + T cell proliferation, triggers TCR activation, and is dispensable for memory CD8 + T cell generation in mice (61). In addition, the interaction of keratinocytes, LCs, and dDCs after cutaneous vaccination tends to promote inflammatory cytokine production, such as IL1-α, IL-6, IL-8, and CXCL10, that might contribute to the overall inflammatory reaction and further promote the attraction of inflammatory cells at the immunization site (62,63). Moreover, vaccine adjuvant monophosphoryl lipid A (MPLA) enables effective CD8 + T cell differentiation into cytotoxic cells in the presence of DC-induced IL-6.…”

Section: Discussionmentioning

confidence: 99%

Innate gene signature distinguishes humoral versus cytotoxic responses to influenza vaccination

Gonçalves¹,

Bonduelle²,

Soria³

et al. 2019

Journal of Clinical Investigation

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METHODS. This randomized phase I/II clinical study (n = 60 healthy subjects aged 18-45 years old) used transcriptomic analysis to discover early biomarkers of immune response quality after transcutaneous (t.c.), intradermal (i.d.), and intramuscular (i.m.) administration of a trivalent influenza vaccine (TIV, season 2012-2013, 1:1:1 ratio). Safety and immunogenicity (hemagglutinin inhibition [HI], microneutralization [MN] antibodies, and CD4+ and CD8+ effector T cells) were measured at baseline day 0 (d0) and at d21. Blood transcriptome was analyzed at d0 and d1. RESULTS. TIV-specific CD8+ granzyme B+ (GRZ) T cells appeared in more individuals immunized by the t.c. and i.d. routes, whereas immunization by the i.d. and i.m. routes prompted high levels of HI antibody titers and MN against A/H1N1 and A/H3N2 influenza viral strains. The early innate gene signature anticipated immunological outcome by discriminating 2 clusters of individuals with either distinct humoral or CD8 cytotoxic responses. Several pathways explained this dichotomy and confirmed that 9 genes and the serum level of CXCL10 were correlated with either TIV-specific cytotoxic CD8+GRZ+ T cell or antibody responses. A logistic regression analysis demonstrated that these 9 genes and the serum levels of CXCL10 at d1/d0 best predicted TIV-specific CD8+GRZ+ T cell and antibody responses at d21. CONCLUSION. This study provides new insight into the impact of immunization routes and innate signature in the quality of adaptive immune responses. TRIAL REGISTRATION. This study has been registered at ClinicalTrials.gov (NCT01707602).

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Section: Discussionmentioning

confidence: 99%

Innate gene signature distinguishes humoral versus cytotoxic responses to influenza vaccination

Gonçalves¹,

Bonduelle²,

Soria³

et al. 2019

Journal of Clinical Investigation

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“…IL-32γ has been described as key molecular link between KCs and Langerhans cells (LC) under steady-state conditions in healthy skin, where it induces the migration of LC from the epidermis into the dermis before they migrate to the draining lymph node ( 6 ). LC and other DC subsets in the skin were shown to express IL-32.…”

Section: The Role Of Il-32 In Healthy Skin and Atopic Dermatitismentioning

confidence: 99%

“…Evidently, IL-32 is upregulated in the skin and serum of AD patients, and serum levels of IL-32 correlate with disease severity, even in patients who respond to treatment. Although IL32 was first identified in activated T and NK cells ( 45 ), current literature suggests that KC appear to be an important source of IL-32 in skin inflammation, particularly in AD ( 6 , 7 ). In addition, IL-32 has been reported to induce apoptosis of KCs.…”

Section: The Role Of Il-32 In Healthy Skin and Atopic Dermatitismentioning

confidence: 99%

“…The initial innate immune response plays a pivotal role in the onset of the disease and the progression of local to systemic inflammation. IL-32 is potentially one of the key cytokines in shaping immune activation and inflammation in the early stages of AD development, as it has the capacity to strongly influence dendritic cell (DC) activation ( 6 ). Lesional skin of AD patients was found to have increased levels of IL-32 ( 7 ).…”

Section: Introductionmentioning

confidence: 99%

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IL-32 as a potential biomarker and therapeutic target in skin inflammation

Wallimann,

Schenk

2023

Front. Immunol.

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IL-32 is a recently described cytokine that performs a variety of functions under inflammatory conditions. Serum IL-32 has been shown to be elevated in several diseases, including type 2 diabetes, cancer, systemic lupus erythematosus, HIV infection, and atopic diseases including atopic dermatitis. There are nine different isoforms of IL-32, with IL-32γ being the most biologically active one. The following review summarizes the different roles of the various IL-32 isoforms in the context of skin inflammation, with a focus on atopic dermatitis.

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“…Focusing on the molecular level, Gonnet et al [64] sought to determine the role of IL-32 produced by keratinocytes on surrounding Langerhans cells. The model used involves HSEs infected with modified vaccinia virus Ankara.…”

Section: The Microbiological Impact Of Bacteria Viruses and Fungi On ...mentioning

confidence: 99%

Emergence of New Concepts in Skin Physiopathology through the Use of in vitro Human Skin Explants Models

Cousin,

Misery,

de Vries

et al. 2023

Dermatology

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Background: This review summarizes uses and new applications for dermatological research of in vitro culture models of human skin explants (HSEs). In the last decade, many innovations have appeared in the literature and an exponential number of studies have been recorded in various fields of application such as process culture engineering, stem cell extractions methodology, or cell-to-cell interaction studies under physiological and pathological conditions, wound-healing, and inflammation. Most studies also concerned pharmacology, cosmetology, and photobiology. However, these topics will not be considered in our review. Summary: A better understanding of the mechanisms driving intercellular relationships, at work in the maintenance of 3D tissue architectures has led to the improvement of cell culture techniques. Many papers have focused on the physiological ways that govern in vitro tissue maintenance of HSEs. The analysis of the necessary mechanical stress, intercellular and cell-matrix interactions, allows the maintenance and prolonged use of HSEs in culture for up to 15 days, regardless of the great variability of study protocols from one laboratory to another and in accordance with the objectives set. Because of their close similarities to fresh skin, HSEs are increasingly used to study skin barrier repair and wound healing physiology. Easy to use in co-culture, this model allows a better understanding of the connections and interactions between the peripheral nervous system, the skin and the immune system. The development of the concept of an integrated neuro-immuno-cutaneous system at work in skin physiology and pathology highlighted by this article represents one of the new technical challenges in the field of in vitro culture of HSE. This review of the literature also reveals the importance of using such models in pathology. As sources of stem cells, HSEs are the basis for the development of new tissue engineering models such as organoids or optical clearing tissues technology. This study identifies the main advances and cross-cutting issues in the use of HSE.

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Interleukin-32 promotes detachment and activation of human Langerhans cells in a human skin explant model

Abstract: We propose, for the first time, that IL-32 is a molecular link between KCs and LCs in healthy skin, provoking LC migration from the epidermis to the dermis prior to their migration to the draining lymph nodes.

Cited by 7 publications

References 38 publications

Innate gene signature distinguishes humoral versus cytotoxic responses to influenza vaccination

Innate gene signature distinguishes humoral versus cytotoxic responses to influenza vaccination

IL-32 as a potential biomarker and therapeutic target in skin inflammation

Emergence of New Concepts in Skin Physiopathology through the Use of in vitro Human Skin Explants Models

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