Dataset Information

Modulation of Skin Inflammatory Responses by Aluminum Adjuvant.

ABSTRACT: Aluminum salt (AS), one of the most commonly used vaccine adjuvants, has immuno-modulatory activity, but how the administration of AS alone may impact the activation of the skin immune system under inflammatory conditions has not been investigated. Here, we studied the therapeutic effect of AS injection on two distinct skin inflammatory mouse models: an imiquimod (IMQ)-induced psoriasis-like model and an MC903 (calcipotriol)-induced atopic dermatitis-like model. We found that injection of a high dose of AS not only suppressed the IMQ-mediated development of T-helper 1 (Th1) and T-helper 17 (Th17) immune responses but also inhibited the IMQ-mediated recruitment and/or activation of neutrophils and macrophages. In contrast, AS injection enhanced MC903-mediated development of the T-helper 2 (Th2) immune response and neutrophil recruitment. Using an in vitro approach, we found that AS treatment inhibited Th1 but promoted Th2 polarization of primary lymphocytes, and inhibited activation of peritoneal macrophages but not bone marrow derived neutrophils. Together, our results suggest that the injection of a high dose of AS may inhibit Th1 and Th17 immune response-driven skin inflammation but promote type 2 immune response-driven skin inflammation. These results may provide a better understanding of how vaccination with an aluminum adjuvant alters the skin immune response to external insults.

SUBMITTER: Liao Y

PROVIDER: S-EPMC9966661 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Modulation of Skin Inflammatory Responses by Aluminum Adjuvant.

Liao Yanhang Y Sun Lixiang L Nie Meifeng M Li Jiacheng J Huang Xiaofen X Heng Shujun S Zhang Wenlu W Xia Tian T Guo Zhuolin Z Zhao Qinjian Q Zhang Ling-Juan LJ

Pharmaceutics 20230208 2

Aluminum salt (AS), one of the most commonly used vaccine adjuvants, has immuno-modulatory activity, but how the administration of AS alone may impact the activation of the skin immune system under inflammatory conditions has not been investigated. Here, we studied the therapeutic effect of AS injection on two distinct skin inflammatory mouse models: an imiquimod (IMQ)-induced psoriasis-like model and an MC903 (calcipotriol)-induced atopic dermatitis-like model. We found that injection of a high ...[more]

PMID: 36839900

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Project description:Macrophages are innate immune cells that interact with complex extracellular matrix environments, which have varied stiffness, composition, and structure, and such interactions can lead to the modulation of cellular activity. Collagen is often used in the culture of immune cells, but the effects of substrate functionalization conditions are not typically considered. Here, we show that the solvent system used to attach collagen onto a hydrogel surface affects its surface distribution and organization, and this can modulate the responses of macrophages subsequently cultured on these surfaces in terms of their inflammatory activation and expression of adhesion and mechanosensitive molecules. Collagen was solubilized in either acetic acid (Col-AA) or N-(2-hydroxyethyl)piperazine-N'-ethanesulfonic acid (HEPES) (Col-HEP) solutions and conjugated onto soft and stiff polyacrylamide (PA) hydrogel surfaces. Bone marrow-derived macrophages cultured under standard conditions (pH 7.4) on the Col-HEP-derived surfaces exhibited stiffness-dependent inflammatory activation; in contrast, the macrophages cultured on Col-AA-derived surfaces expressed high levels of inflammatory cytokines and genes, irrespective of the hydrogel stiffness. Among the collagen receptors that were examined, leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) was the most highly expressed, and knockdown of the Lair-1 gene enhanced the secretion of inflammatory cytokines. We found that the collagen distribution was more homogeneous on Col-AA surfaces but formed aggregates on Col-HEP surfaces. The macrophages cultured on Col-AA PA hydrogels were more evenly spread, expressed higher levels of vinculin, and exerted higher traction forces compared to those of cells on Col-HEP. These macrophages on Col-AA also had higher nuclear-to-cytoplasmic ratios of yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), key molecules that control inflammation and sense substrate stiffness. Our results highlight that seemingly slight variations in substrate deposition for immunobiology studies can alter critical immune responses, and this is important to elucidate in the broader context of immunomodulatory biomaterial design.

Dataset Information

Modulation of Skin Inflammatory Responses by Aluminum Adjuvant.

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Modulation of Skin Inflammatory Responses by Aluminum Adjuvant.

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