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Contact Dermatitis Dec 2023Allergic contact dermatitis (ACD) is an inflammatory disease with a complex pathophysiology in which epidermal-resident memory CD8 T (T ) cells play a key role. The...
BACKGROUND
Allergic contact dermatitis (ACD) is an inflammatory disease with a complex pathophysiology in which epidermal-resident memory CD8 T (T ) cells play a key role. The mechanisms involved in the activation of CD8 T cells during allergic flare-up responses are not understood.
METHODS
The expression of CD100 and its ligand Plexin B2 on CD8 T cells and keratinocytes before and after allergen exposure was determined by flow cytometry and RT-qPCR. The role of CD100 in the inflammatory response during the challenge phase of ACD was determined in a model of ACD in CD100 knockout and wild-type mice.
RESULTS
We show that CD8 T cells express CD100 during homeostatic conditions and up-regulate it following re-exposure of allergen-experienced skin to the experimental contact allergen 1-fluoro-2,4-dinitrobenzene (DNFB). Furthermore, Plexin B2 is up-regulated on keratinocytes following exposure to some contact allergens. We show that loss of CD100 results in a reduced inflammatory response to DNFB with impaired production of IFNγ, IL-17A, CXCL1, CXCL2, CXCL5, and IL-1β and decreased recruitment of neutrophils to the epidermis.
CONCLUSION
Our study demonstrates that CD100 is expressed on CD8 T cells and is required for full activation of CD8 T cells and the flare-up response of ACD.
Topics: Animals; Mice; Allergens; Dermatitis, Allergic Contact; Dinitrofluorobenzene; Keratinocytes; Skin
PubMed: 37700557
DOI: 10.1111/cod.14414 -
International Journal of Molecular... Aug 2023(L.) S. has been used to treat epidemic fever, dysuria, and various skin ailments, such as measles eruptions, eczema, and pruritus, in China, Japan, and Korea. In this...
(L.) S. has been used to treat epidemic fever, dysuria, and various skin ailments, such as measles eruptions, eczema, and pruritus, in China, Japan, and Korea. In this study, the active compounds in and their target genes were identified by network-based analysis. Moreover, the study evaluated the effects of a 70% ethanolic extract of (EESP) on skin lesions, histopathological changes, inflammatory cytokines, and chemokines in mice with contact dermatitis (CD) induced by 1-fluoro-2,4-dinitrobenzene (DNFB), and examined the inhibitory effects of EESP on mitogen-activated protein kinase (MAPK) signalling pathways. In our results, 14 active compounds and 29 CD-related target genes were identified. Among them, tumour necrosis factor (TNF) and interleukin 6 (IL-6) were identified as hub genes, and luteolin and apigenin showed a strong binding affinity with TNF (<-8 kcal/mol) and IL-6 (<-6 kcal/mol). Our in vivo studies showed that topical EESP ameliorated DNFB-induced skin lesions and histopathological abnormalities, and reduced the levels of TNF-α, interferon (IFN)-ɣ, IL-6, and monocyte chemotactic protein (MCP)-1 in inflamed tissues. In conclusion, our findings suggest the potential for dermatological applications of and suggest that its anti-dermatitis action is related to the inhibition of TNF and IL-6 by luteolin and luteolin glycosides.
Topics: Animals; Mice; Dinitrofluorobenzene; Interleukin-6; Luteolin; Dermatitis, Contact; Tumor Necrosis Factor-alpha; Araceae; Dinitrobenzenes; Anti-Inflammatory Agents; Plant Extracts
PubMed: 37686078
DOI: 10.3390/ijms241713271 -
Biochemical and Biophysical Research... Oct 2023Allergic contact dermatitis (ACD) and atopic dermatitis (AD) are common inflammatory diseases. We previously reported attenuated contact hypersensitivity (CHS) responses...
Tolerogenic phenotype of dendritic cells is induced after hapten sensitization followed by attenuated contact hypersensitivity response in atopic dermatitis model NC/Nga mice.
Allergic contact dermatitis (ACD) and atopic dermatitis (AD) are common inflammatory diseases. We previously reported attenuated contact hypersensitivity (CHS) responses in AD model mice using 2,4-dinitrofluorobenzene, reflecting clinical experiments. However, previous studies have not addressed the commonality of findings across haptens and mechanisms focused on dendritic cells (DCs). Thus, this study evaluated CHS responses to fluorescein isothiocyanate (FITC) and DC migration and maturation in the sensitization phase of CHS in AD. CHS responses to FITC were compared between NC/Nga mice without and with AD induction (non-AD and AD mice, respectively). T-cell responses and DC migration and maturation after FITC-induced sensitization were examined in the draining lymph nodes of non-AD and AD mice. AD mice demonstrated reduced CHS responses to FITC under decreased T-cell proliferation following sensitization and interferon-γ production by hapten-specific T cells compared with non-AD mice. In addition, the number of FITCCD11cMHC class II migratory DCs 24 h after FITC sensitization was comparable between non-AD and AD mice. However, FITCCD11cMHC class II migratory DCs in AD mice exhibited lower expression levels of CD80 and CD86 and higher expression levels of PD-L1 and mRNA of transforming growth factor beta than non-AD mice. These findings suggest that attenuated CHS responses may be hapten-independent and the induction of the tolerogenic phenotype of hapten-bearing DCs can contribute to reduced T-cell proliferation after sensitization and CHS responses in AD.
Topics: Mice; Animals; Dermatitis, Atopic; Fluorescein-5-isothiocyanate; Phenotype; Fluorescein; Haptens; Dermatitis, Contact; Dendritic Cells
PubMed: 37611349
DOI: 10.1016/j.bbrc.2023.08.042 -
Allergy Jan 2024Tissue-resident memory T (T ) cells are detrimental in allergic contact dermatitis (ACD), in which they contribute to the chronicity and severity of the disease.
BACKGROUND
Tissue-resident memory T (T ) cells are detrimental in allergic contact dermatitis (ACD), in which they contribute to the chronicity and severity of the disease.
METHODS
We assessed the impact of a standard topical corticosteroid (TCS) treatment, triamcinolone acetonide (TA), on the formation, maintenance and reactivation of epidermal T cells in a preclinical model of ACD to 2,4-dinitrofluorobenzene. TA 0.01% was applied at different time points of ACD response and we monitored skin inflammation and tracked CD8+ CD69+ CD103+ T by flow cytometry and RNA sequencing.
RESULTS
The impact of TA on T formation depended on treatment regimen: (i) in a preventive mode, that is, in sensitized mice before challenge, TA transiently inhibited the infiltration of effector T cells and the accumulation of T upon hapten challenge. In contrast, (ii) in a curative mode, that is, at the peak of the ACD response, TA blocked skin inflammation but failed to prevent the formation of T . Finally, (iii) in a proactive mode, that is, on previous eczema lesions, TA had no effect on the survival of skin T , but transiently inhibited their reactivation program upon allergen reexposure. Indeed, specific T progressively regained proliferative functions upon TA discontinuation and expanded in the tissue, leading to exaggerated iterative responses. Interestingly, T re-expansion correlated with the decreased clearance of hapten moieties from the skin induced by repeated TA applications.
CONCLUSIONS
Our results demonstrate that TCS successfully treat ACD inflammation, but are mostly ineffective in impeding the formation and expansion of allergen-specific T , which certainly restricts the induction of lasting tolerance in patients with chronic dermatitis.
Topics: Humans; Mice; Animals; Memory T Cells; CD8-Positive T-Lymphocytes; Skin; Dermatitis, Allergic Contact; Dermatitis, Atopic; Allergens; Inflammation; Dermatologic Agents; Haptens; Adrenal Cortex Hormones; Immunologic Memory
PubMed: 37539746
DOI: 10.1111/all.15819 -
Research Square Jul 2023Nanoparticle (NP) skin exposure is linked to the increased prevalence of allergic contact dermatitis. In prior studies using the mouse contact hypersensitivity (CHS)...
Nanoparticle (NP) skin exposure is linked to the increased prevalence of allergic contact dermatitis. In prior studies using the mouse contact hypersensitivity (CHS) model, we reported that silica 20 nm (Si20nm) suppressed the allergic response and TiO2 doped with manganese (mTiO2) exacerbated it. In this work, we conducted in vitro experiments using bone marrow-derived dendritic cells (BMDCs) to study the combinatorial effect of the potent 2, 4-dinitrofluorobenzene (DNFB) hapten sensitizer with Si20nm and mTiO2 NPs on BMDC cytotoxicity, cytokine secretion and phenotype using the B7 family ligands. Results show that DNFB and mTiO2 behave similarly and exhibit proinflammatory characteristics while Si20nm promotes a naive phenotype. We observe that the B7-H3 (CD276) ligand is only expressed on CD80+ (B7-1) BMDC. Results from adoptive transfer CHS studies, combined with BMDC phenotype analysis, point to the importance of PD-L2 expression in modulating the adaptive immune response. This work identifies metrics that can be used to predict the effects of NPs on contact allergy and to guide efforts to engineer cell-based therapies to induce antigen specific immune tolerance.
PubMed: 37503107
DOI: 10.21203/rs.3.rs-3069059/v1 -
Contact Dermatitis Oct 2023Poly(I:C) is recognised by endosomal Toll-like receptor 3 (TLR3) and activates cytotoxic CD8(+) lymphocytes and natural killer (NK) cells. It has been shown that the...
INTRODUCTION
Poly(I:C) is recognised by endosomal Toll-like receptor 3 (TLR3) and activates cytotoxic CD8(+) lymphocytes and natural killer (NK) cells. It has been shown that the viral TLR3 agonist induces robust and long-lasting T-cell-mediated responses. In addition, TLR3 modulates the contact hypersensitivity reaction.
OBJECTIVE
This study aimed to determine whether poly(I:C) injection can induce NK-mediated hapten reactivity in mice.
METHODS
Mice were treated with poly(I:C), and their response to dinitrofluorobenzene hapten was measured by assessing ear swelling and serum interferon gamma (IFN-γ) production. Adoptive cell transfer and cell sorting were used to investigate the mechanism of the reaction, and the phenotype of poly(I:C)-activated liver NK cells was determined by flow cytometry analysis.
RESULTS
The results showed that poly(I:C) administration increased ear swelling, serum IFN-γ levels and the response to hapten in both immunocompetent and T- and B-cell-deficient mice. Only liver poly(I:C)-activated DX5(+) NK cells were able to transfer reactivity to hapten into a naive recipient. Induction of liver NK cells after poly(I:C) administration was TLR3/TRIF- and IFN-γ-dependent, interleukin 12-independent, and not modulated by MyD88.
CONCLUSION
This study provides new insights into how poly(I:C) stimulates NK-mediated reactivity to hapten and suggests that liver NK cells may modulate the immune response to non-pathogenic factors during viral infection.
Topics: Mice; Animals; Toll-Like Receptor 3; Ligands; Dermatitis, Allergic Contact; Killer Cells, Natural; Poly I-C; Interferon-gamma; Mice, Inbred C57BL
PubMed: 37463838
DOI: 10.1111/cod.14380 -
Frontiers in Immunology 2023Major histocompatibility complex (MHC) class Ib molecules present antigens to subsets of T cells primarily involved in host defense against pathogenic microbes and...
Major histocompatibility complex (MHC) class Ib molecules present antigens to subsets of T cells primarily involved in host defense against pathogenic microbes and influence the development of immune-mediated diseases. The MHC class Ib molecule MHC-related protein 1 (MR1) functions as a platform to select MR1-restricted T cells, including mucosal-associated invariant T (MAIT) cells in the thymus, and presents ligands to them in the periphery. MAIT cells constitute an innate-like T-cell subset that recognizes microbial vitamin B metabolites and plays a defensive role against microbes. In this study, we investigated the function of MR1 in allergic contact dermatitis (ACD) by examining wild-type (WT) and MR1-deficient (MR1) mice in which ACD was induced with 2,4-dinitrofluorobenzene (DNFB). MR1 mice exhibited exaggerated ACD lesions compared with WT mice. More neutrophils were recruited in the lesions in MR1 mice than in WT mice. WT mice contained fewer MAIT cells in their skin lesions following elicitation with DNFB, and MR1 mice lacking MAIT cells exhibited a significant increase in IL-17-producing αβ and γδ T cells in the skin. Collectively, MR1 mice displayed exacerbated ACD from an early phase with an enhanced type 3 immune response, although the precise mechanism of this enhancement remains elusive.
Topics: Animals; Mice; Dermatitis, Allergic Contact; Dinitrofluorobenzene; Histocompatibility Antigens Class I; Interleukin-17; Minor Histocompatibility Antigens
PubMed: 37409131
DOI: 10.3389/fimmu.2023.1215478 -
Indian Journal of Dermatology 2023This study aims to investigate the anti-inflammatory effects of cinnamaldehyde in atopic dermatitis (AD) in the mouse model.
BACKGROUND
This study aims to investigate the anti-inflammatory effects of cinnamaldehyde in atopic dermatitis (AD) in the mouse model.
MATERIALS AND METHODS
Twenty-four mice were divided into four groups: Group A (control), group B [AD with no treatment (AD + NoTre)], group C [AD with corticosteroids (AD + Cort)] and group D [AD with cinnamaldehyde (AD + Cin)]. 2,4-dinitrofluorobenzene was used to form the AD model. Topical corticosteroid was applied to group C, and oral cinnamaldehyde was administered to group D. Dorsal skin biopsies were evaluated immunohistochemically with interleukin (IL)-25, IL-33, thymic stromal lymphopoietin and caspase-3.
RESULTS
Epithelial thicknesses were significantly higher in group B-D mice compared to group A ( = 0.002, 0.009, 0.004, respectively). Significantly, higher staining with IL-25 was observed in group B (AD + NoTre) and group D (AD + Cin) than in group A (control) ( = 0.003, 0.002, respectively). However, no significant difference was observed between group D (AD + Cin) and group B (AD + NoTre). All three groups (B-D) had significantly higher staining in terms of diffuseness of IL-33 compared to group A (control) ( = 0.002, 0.002, 0.002, respectively). Caspase-3 staining was significantly lower in group D (AD + Cin) than in group B (AD + NoTre) ( = 0.003, 0.002, respectively). Moreover, caspase-3 staining intensity was significantly lower in group D (AD + Cin) than in group C (AD + Cort) ( = 0.002).
CONCLUSIONS
Our study demonstrated that IL-33, IL-25 and caspase-3 have a role in the pathogenesis of AD. Furthermore, cinnamaldehyde reduced caspase-3 activity more than topical corticosteroids and anti-inflammatory effects might be investigated in AD therapy with future studies.
PubMed: 37275806
DOI: 10.4103/ijd.ijd_576_22 -
Experimental and Therapeutic Medicine Jul 2023polysaccharides (MCPs) have been reported to exert beneficial roles, such as disease healing, in medicine and pharmacy. However, little is known about their effects on...
polysaccharides (MCPs) have been reported to exert beneficial roles, such as disease healing, in medicine and pharmacy. However, little is known about their effects on immunomodulation The present study aimed to explore the possible effects of polysaccharide (MCP) on the immunomodulatory activity of mice lymphocytes. To this aim, male BALB/c mice aged 6-8 weeks were assigned to the following six experimental groups: i) Normal (NG); ii) model (MG); iii) positive (PG); iv) MCP low-dose (MLG); v) MCP medium-dose (MMG); and vi) MCP high-dose (MHG). An immunosuppressive model was established by the intraperitoneal injection of cyclophosphamide in all groups apart from NG. The NG and MG mice were fed with distilled water, whereas the PG mice were administered with levamisole and the MLG, MMG and MHG mice were fed on low, medium and high (100, 200 and 300 mg/kg, respectively) doses of MCP for 21 consecutive days. Subsequently, the mice underwent surgical procedure and were analysed using a range of procedures, including measurement of the thymus index (TI) and spleen index (SI), assessment of the lymphocyte proliferation rate and cell phagocytosis of peritoneal macrophages, lymphocyte proliferation, secretion and mRNA expression of cytokines IFN-γ, IL-6 and IL-12. The mice divided into six groups as mentioned above and treated for 7 days, in the first 6 days, except NG group, mice in each group were desiccated in the abdominal cavity and sensitized by 1% dinitrofluorobenzene (DNFB). On day 6, mice were sensitized with 20 µl DNFB/acetone/olive oil solution behind the right ear and in front of the right ear. Compared with those in the NG mice (not injected with 80 mg/kg cyclophosphamide), the TIs and SIs of the PG, MLG, MMG and MHG mice were increased. In addition, the inhibitory rate of ear swelling and the phagocytic activity of peritoneal macrophages in the PG, MLG, MMG and MHG mice were increased compared with those of MG. Furthermore, the lymphocyte proliferation rate, the secretion and relative mRNA expression levels of cytokines IFN-γ, IL-6 and IL-12 were significantly increased in the PG, MMG and MHG mice compared with those in the NG mice. The results from the present study suggest that treatment with MCP led to an upregulation of the organ indices of immunosuppressed mice, reduced their delayed allergic reaction indicated by the differential cytokine levels, improved the phagocytic activity of peritoneal macrophages, enhanced the proliferation rate of lymphocytes, increased the secretion and expression of IFN-γ, IL-6 and IL-12. Therefore, MCP may improve the immune function of the immunosuppressed mice.
PubMed: 37273762
DOI: 10.3892/etm.2023.12006 -
Spectrochimica Acta. Part A, Molecular... Nov 2023The homeostasis of biothiols is closely related to the health of organisms. In view of the important role of biothiols, a fluorescent probe (7HIN-D) for the detection of...
The homeostasis of biothiols is closely related to the health of organisms. In view of the important role of biothiols, a fluorescent probe (7HIN-D) for the detection of intracellular biothiols was developed based on a simple chalcone fluorophore 7HIN with "ESIPT + AIE" characteristics. The probe 7HIN-D was obtained by introducing a biothiols specific DNBS (2,4-dinitrobenzenesulfonyl) unit as a fluorescence quencher to the fluorophore 7HIN. The nucleophilic substitution reaction between biothiols and probe 7HIN-D will release the DNBS unit and the fluorophore 7HIN, which exhibits a "turn on" AIE fluorescence with a large Stokes shift of 113 nm. The probe 7HIN-D displays high sensitivity and good selectivity to biothiols, and the detection limits value of probe 7HIN-D for GSH, Cys and Hcy were 0.384 μmol/L, 0.471 μmol/L and 0.638 μmol/L, respectively. In addition, the probe has been successfully used for fluorescence detection of endogenous biothiols in living cells due to its excellent performance, good biocompatibility and low cytotoxicity.
Topics: Humans; Fluorescent Dyes; Chalcones; Spectrometry, Fluorescence; HeLa Cells; Cysteine; Glutathione; Homocysteine
PubMed: 37216722
DOI: 10.1016/j.saa.2023.122870