Huangbai Liniment Ameliorates Skin Inflammation in Atopic Dermatitis

Atopic dermatitis (AD), also known as atopic eczema, is one of the most common skin diseases and is characterized by allergic skin inflammation, redness, and itchiness and is associated with a hyperactivated type 2 immune response. The leading causes of AD include an imbalance in the immune system, genetic predisposition, or environmental factors, making the development of effective pharmacotherapies complex. Steroids are widely used to treat AD; however, they provide limited efficacy in the long term and can lead to adverse effects. Thus, novel treatments that offer durable efficacy and fewer side effects are urgently needed. Here, we investigated the therapeutic potential of Huangbai Liniment (HB), a traditional Chinese medicine, using an experimental AD mouse model, following our clinical observations of AD patients. In both AD patient and the mouse disease model, HB significantly improved the disease condition. Specifically, patients who received HB treatment on local skin lesions (3–4 times/day) showed improved resolution of inflammation. Using the 1-Chloro-2,4-dinitrobenzene (DNCB)-induced AD model in BALB/c mice, we observed that HB profoundly alleviated severe skin inflammation and relieved the itching. The dermatopathological results showed markedly reversed skin inflammation with decreased epidermal thickness and overall cellularity. Correspondingly, HB treatment largely decreased the mRNA expression of proinflammatory cytokines, including IL-1β, TNF-α, IL-17, IL-4, and IL-13, associated with declined gene expression of IL-33, ST2, and GATA3, which are connected to the type 2 immune response. In addition, HB restored immune tolerance by promoting regulatory T (TREG) cells and inhibiting the generation of TH1, TH2, and TH17 cells in vitro and in the DNCB-induced AD mouse model. For the first time, we demonstrate that HB markedly mitigates skin inflammation in AD patients and the DNCB-induced AD mouse model by reinvigorating the T cell immune balance, shedding light on the future development and application of novel HB-based therapeutics for AD.

Download Full-text

The extracellular serine protease from Staphylococcus epidermidis elicits a type 2 immune response in atopic dermatitis patients

10.22541/au.162443212.25847373/v1 ◽

2021 ◽

Author(s):

Goran Abdurrahman ◽

Rebecca Pospich ◽

Leif Steil ◽

Manuela Gesell Salazar ◽

Juan Izquierdo González ◽

...

Keyword(s):

Mass Spectrometry ◽

Immune Response ◽

T Cells ◽

Atopic Dermatitis ◽

Serine Protease ◽

Staphylococcus Epidermidis ◽

Type 2 Immune Response ◽

Ifn Γ ◽

Extracellular Serine Protease

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease caused by skin barrier defects and a misdirected type 2 immune response against antigens. The skin microbiome in AD is characterised by a reduction in microbial diversity with a dominance of staphylococci, including Staphylococcus epidermidis (S. epidermidis). To assess whether S. epidermidis antigens play a role in AD, we studied the immune response against the extracellular serine protease (Esp). Methods: We analyzed the binding of human IgG4 to S. epidermidis extracellular proteins using immunoblotting and mass spectrometry. We then measured serum antibodies specific for recombinant Esp by ELISA in healthy and AD individuals. We also stimulated T cells from AD patients and control subjects with Esp and measured the secreted cytokines. Finally, we analyzed the proteolytic activity of Esp against IL-33 and determined the cleavage sites by mass spectrometry. Results: We identified Esp as the dominant IgG4-binding antigen of S. epidermidis. Esp-specific IgE was present in human serum; AD patients had higher concentrations than controls. The T cell response to Esp in healthy adults was characterized by IL-17, IL-22, IFN-γ, and IL-10, whereas the AD patients’ T cells lacked IL-17 production and released only low amounts of IL-22, IFN-γ, and IL-10. In contrast, Th2 cytokine release was higher in T cells from AD patients than from healthy controls. Mature Esp cleaved and activated the alarmin IL-33. Conclusions: Esp elicits type 2-biased response in AD patients. This suggests that S. epidermidis can aggravate AD through the allergenic properties of Esp.

Download Full-text

A non-canonical type 2 immune response coordinates tuberculous granuloma formation and epithelialization

Cell ◽

10.1016/j.cell.2021.02.046 ◽

2021 ◽

Author(s):

Mark R. Cronan ◽

Erika J. Hughes ◽

W. Jared Brewer ◽

Gopinath Viswanathan ◽

Emily G. Hunt ◽

...

Keyword(s):

Immune Response ◽

Granuloma Formation ◽

Type 2 Immune Response ◽

Tuberculous Granuloma ◽

Canonical Type

Download Full-text

Herpes simplex virus 1 proteins can induce skin inflammation in an atopic dermatitis‐like mouse model

Experimental Dermatology ◽

10.1111/exd.14327 ◽

2021 ◽

Author(s):

Natalija Novak ◽

Heike Weighardt ◽

Rafael Valdelvira ◽

Elena Izquierdo ◽

Irmgard Förster ◽

...

Keyword(s):

Atopic Dermatitis ◽

Herpes Simplex Virus ◽

Herpes Simplex ◽

Mouse Model ◽

Skin Inflammation ◽

Herpes Simplex Virus 1 ◽

Simplex Virus

Download Full-text

Dairy Heifers Naturally Exposed toFasciola hepaticaDevelop a Type 2 Immune Response and Concomitant Suppression of Leukocyte Proliferation

Infection and Immunity ◽

10.1128/iai.00607-17 ◽

2017 ◽

Vol 86 (1) ◽

Cited By ~ 3

Author(s):

John Graham-Brown ◽

Catherine Hartley ◽

Helen Clough ◽

Aras Kadioglu ◽

Matthew Baylis ◽

...

Keyword(s):

Immune Response ◽

Immune Responses ◽

Peripheral Blood ◽

Serum Antibody ◽

Enzyme Linked Immunosorbent Assay ◽

Mixed Effect ◽

Content Type ◽

Grazing Season ◽

Type 2 Immune Response

ABSTRACTFasciola hepaticais a parasitic trematode of global importance in livestock. Control strategies reliant on anthelmintics are unsustainable due to the emergence of drug resistance. Vaccines are under development, but efficacies are variable. Evidence from experimental infection suggests that vaccine efficacy may be affected by parasite-induced immunomodulation. Little is known about the immune response toF. hepaticafollowing natural exposure. Hence, we analyzed the immune responses over time in calves naturally exposed toF. hepaticainfection. Cohorts of replacement dairy heifer calves (n= 42) with no prior exposure toF. hepatica, on three commercial dairy farms, were sampled over the course of a grazing season. Exposure was determined through anF. hepatica-specific serum antibody enzyme-linked immunosorbent assay (ELISA) and fluke egg counts. Concurrent changes in peripheral blood leukocyte subpopulations, lymphocyte proliferation, and cytokine responses were measured. Relationships between fluke infection and immune responses were analyzed by using multivariable linear mixed-effect models. All calves from one farm showed evidence of exposure, while cohorts from the remaining two farms remained negative over the grazing season. A type 2 immune response was associated with exposure, with increased interleukin-4 (IL-4) production, IL-5 transcription, and eosinophilia. Suppression of parasite-specific peripheral blood mononuclear cell (PBMC) proliferation was evident, while decreased mitogen-stimulated gamma interferon (IFN-γ) production suggested immunomodulation, which was not restricted to parasite-specific responses. Our findings show that the global immune response is modulated toward a nonproliferative type 2 state following natural challenge withF. hepatica. This has implications in terms of the timing of the administration of vaccination programs and for host susceptibility to coinfecting pathogens.

Download Full-text

Macrophage-Derived Osteopontin Influences the Amplification of Cryptococcus neoformans–Promoting Type 2 Immune Response

The Journal of Immunology ◽

10.4049/jimmunol.2100202 ◽

2021 ◽

pp. ji2100202

Author(s):

Adithap Hansakon ◽

Chin Wen Png ◽

Yongliang Zhang ◽

Pornpimon Angkasekwinai

Keyword(s):

Immune Response ◽

Cryptococcus Neoformans ◽

Type 2 Immune Response

Download Full-text

Erratum for Graham-Brown et al., “Dairy Heifers Naturally Exposed to Fasciola hepatica Develop a Type 2 Immune Response and Concomitant Suppression of Leukocyte Proliferation”

Infection and Immunity ◽

10.1128/iai.00247-18 ◽

2018 ◽

Vol 86 (6) ◽

Cited By ~ 2

Author(s):

John Graham-Brown ◽

Catherine Hartley ◽

Helen Clough ◽

Aras Kadioglu ◽

Matthew Baylis ◽

...

Keyword(s):

Immune Response ◽

Fasciola Hepatica ◽

Dairy Heifers ◽

Type 2 Immune Response

Download Full-text

NK cell recruitment limits tissue damage during an enteric helminth infection

Mucosal Immunology ◽

10.1038/s41385-019-0231-8 ◽

2019 ◽

Vol 13 (2) ◽

pp. 357-370 ◽

Cited By ~ 2

Author(s):

Maria E. Gentile ◽

Yue Li ◽

Amicha Robertson ◽

Kathleen Shah ◽

Ghislaine Fontes ◽

...

Keyword(s):

Immune Response ◽

Nk Cells ◽

Helminth Infection ◽

Nk Cell ◽

Early Response ◽

Cell Recruitment ◽

Parasitic Helminths ◽

Cxcr3 Expression ◽

Type 2 Immune Response

AbstractParasitic helminths cause significant damage as they migrate through host tissues to complete their life cycle. While chronic helminth infections are characterized by a well-described Type 2 immune response, the early, tissue-invasive stages are not well understood. Here we investigate the immune pathways activated during the early stages of Heligmosomoides polygyrus bakeri (Hpb), a natural parasitic roundworm of mice. In contrast to the Type 2 immune response present at later stages of infection, a robust Type 1 immune signature including IFNg production was dominant at the time of parasite invasion and granuloma formation. This early response was associated with an accumulation of activated Natural Killer (NK) cells, with no increase of other innate lymphoid cell populations. Parabiosis and confocal microscopy studies indicated that NK cells were recruited from circulation to the small intestine, where they surrounded parasitic larvae. NK cell recruitment required IFNγ receptor signaling, but was independent of CXCR3 expression. The depletion of tissue-infiltrating NK cells altered neither worm burden nor parasite fitness, but increased vascular injury, suggesting a role for NK cells in mediating tissue protection. Together, these data identify an unexpected role for NK cells in promoting disease tolerance during the invasive stage of an enteric helminth infection.

Download Full-text

Effect of the Lactococcus Lactis 11/19-B1 Strain on Atopic Dermatitis in a Clinical Test and Mouse Model

Nutrients ◽

10.3390/nu12030763 ◽

2020 ◽

Vol 12 (3) ◽

pp. 763 ◽

Cited By ~ 2

Author(s):

Takato Suzuki ◽

Kyoko Nishiyama ◽

Koji Kawata ◽

Kotaro Sugimoto ◽

Masato Isome ◽

...

Keyword(s):

Atopic Dermatitis ◽

Mouse Model ◽

Lactococcus Lactis ◽

Skin Lesions ◽

T Cell Subsets ◽

Eosinophil Infiltration ◽

Clinical Test ◽

Host Immune System ◽

Cervical Lymph Nodes ◽

Ad Mouse Model

Some lactic acid bacteria (LAB) are known to improve atopic dermatitis (AD) through the regulation and stimulation of the host immune system. In this study, we found that ingestion of yogurt containing Lactococcus lactis 11/19-B1 strain (L. lactis 11/19-B1) daily for 8 weeks significantly improved the severity scoring of atopic dermatitis (SCORAD) system score from 38.8 ± 14.4 to 24.2 ± 12.0 in children suffering from AD. We tried to identify which LAB species among the five species contained in the test yogurt contributed to the improvement in AD pathology using an AD mouse model induced by repeated application of 1-fluoro-2, 4-dinitrobenzene (DNFB). AD-like skin lesions on the dorsal skin and ear were most improved by L. lactis 11/19-B1 intake among the five LAB species. In addition, analysis of CD4+ T cell subsets in Peyer’s patches (PPs) and cervical lymph nodes (CLNs) indicated that the intake of L. lactis 11/19-B1 generally suppressed all subsets related to inflammation, i.e., Th1, Th2 and Th17, instead of activating the suppressive system, Treg, in the AD mouse model. Histological observations showed ingestion of L. lactis 11/19-B1 significantly suppressed severe inflammatory findings, such as inflammatory cell filtration, epidermal erosion and eosinophil infiltration. These results suggest that the immunomodulatory effects of L. lactis 11/19-B1 contribute to improvements in AD pathology.

Download Full-text