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- Ottman, N, et al.
(författare)
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Reply
- 2019
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Ingår i: The Journal of allergy and clinical immunology. - : Elsevier BV. - 1097-6825 .- 0091-6749. ; 144:4, s. 1139-1140
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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- Anthoni, M, et al.
(författare)
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Smad3 regulates dermal cytokine and chemokine expression and specific antibody production in murine responses to a respiratory chemical sensitizer
- 2010
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Ingår i: International archives of allergy and immunology. - : S. Karger AG. - 1423-0097 .- 1018-2438. ; 151:2, s. 155-167
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background:</i> The cytokine transforming growth factor-β(TGF-β) has important regulatory roles in the immune system. To investigate the role of intact TGF-β signaling during the contact hypersensitivity (CHS) response to a respiratory allergen, we exposed Smad3–/– mice to topical trimellitic anhydride (TMA). <i>Methods:</i> CHS was induced by topical application of TMA. The swelling of the TMA-exposed ears was analyzed, and lymph node, ear tissue and skin biopsies were collected for RNA isolation, histology and histochemical analyses. Lymph node cell proliferation was measured and blood samples were collected for analysis of TMA-specific immunoglobulin. <i>Results:</i> Topical TMA exposure resulted in increased mRNA expression of proinflammatory and suppressive cytokines (IL-1β, TNF-α, IL-6, IFN-γ, IL-4, IL-10, IL-17, IL-23, TGF-β), chemokines (CXCL9, CXCL10, CCL24) and chemokine receptors (CCR7, CCR8, CXCR2), increased numbers of CD3+ T cells in ear tissue, and lymphadenopathy in the Smad3–/– mice. The IL-10 result was confirmed at the protein level by immunohistochemistry. However, the ear-swelling response and infiltration of eosinophils, F4/80+ cells, CD11c+ cells and mast cells were similar in the Smad3–/– mice compared to their wild-type (WT) siblings. While TMA-specific IgE was induced equally in the WT and Smad3–/– mice, the concentration of TMA-specific IgG2a was significantly lower in the Smad3–/– mice. <i>Conclusions:</i> The Smad3 molecule contributes significantly to the regulation of the cytokine and chemokine network during the CHS response to TMA. The lack of Smad3 resulted in a potent Th2 shift, confirmed by strongly impaired IgG2a levels.
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- Fyhrquist, N, et al.
(författare)
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Microbe-host interplay in atopic dermatitis and psoriasis
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4703-
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Tidskriftsartikel (refereegranskat)abstract
- Despite recent advances in understanding microbial diversity in skin homeostasis, the relevance of microbial dysbiosis in inflammatory disease is poorly understood. Here we perform a comparative analysis of skin microbial communities coupled to global patterns of cutaneous gene expression in patients with atopic dermatitis or psoriasis. The skin microbiota is analysed by 16S amplicon or whole genome sequencing and the skin transcriptome by microarrays, followed by integration of the data layers. We find that atopic dermatitis and psoriasis can be classified by distinct microbes, which differ from healthy volunteers microbiome composition. Atopic dermatitis is dominated by a single microbe (Staphylococcus aureus), and associated with a disease relevant host transcriptomic signature enriched for skin barrier function, tryptophan metabolism and immune activation. In contrast, psoriasis is characterized by co-occurring communities of microbes with weak associations with disease related gene expression. Our work provides a basis for biomarker discovery and targeted therapies in skin dysbiosis.
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- Fyhrquist-Vanni, N, et al.
(författare)
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Contact dermatitis
- 2007
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Ingår i: Dermatologic clinics. - : Elsevier BV. - 0733-8635. ; 25:4, s. 613-
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Tidskriftsartikel (refereegranskat)
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- Haahtela, T, et al.
(författare)
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A short history from Karelia study to biodiversity and public health interventions
- 2023
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Ingår i: Frontiers in allergy. - : Frontiers Media SA. - 2673-6101. ; 4, s. 1152927-
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Tidskriftsartikel (refereegranskat)abstract
- Contact with natural environments enriches the human microbiome, promotes immune balance and protects against allergies and inflammatory disorders. In Finland, the allergy & asthma epidemic became slowly visible in mid 1960s. After the World War II, Karelia was split into Finnish and Soviet Union (now Russia) territories. This led to more marked environmental and lifestyle changes in the Finnish compared with Russian Karelia.The Karelia Allergy Study 2002–2022showed that allergic conditions were much more common on the Finnish side. The Russians had richer gene-microbe network and interaction than the Finns, which associated with better balanced immune regulatory circuits and lower allergy prevalence. In the Finnish adolescents, a biodiverse natural environment around the homes associated with lower occurrence of allergies. Overall, the plausible explanation of the allergy disparity was the prominent change in environment and lifestyle in the Finnish Karelia from 1940s to 1980s. The nationwideFinnish Allergy Programme 2008–2018implemented the biodiversity hypothesis into practice by endorsing immune tolerance, nature contacts, and allergy health with favorable results. A regional health and environment programme,Nature Step to Health 2022–2032, has been initiated in the City of Lahti, EU Green Capital 2021. The programme integrates prevention of chronic diseases (asthma, diabetes, obesity, depression), nature loss, and climate crisis in the spirit ofPlanetary Health. Allergic diseases exemplify inappropriate immunological responses to natural environment. Successful management of the epidemics of allergy and other non-communicable diseases may pave the way to improve human and environmental health.
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- Karisola, P, et al.
(författare)
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Integrative Transcriptomics Reveals Activation of Innate Immune Responses and Inhibition of Inflammation During Oral Immunotherapy for Egg Allergy in Children
- 2021
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Ingår i: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 12, s. 704633-
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Tidskriftsartikel (refereegranskat)abstract
- We previously reported the results of a randomized, open-label trial of egg oral immunotherapy (OIT) in 50 children where 44% were desensitized and 46% were partially desensitized after 8 months of treatment. Here we focus on cell-mediated molecular mechanisms driving desensitization during egg OIT. We sought to determine whether changes in genome-wide gene expression in blood cells during egg OIT correlate with humoral responses and the clinical outcome. The blood cell transcriptome of 50 children receiving egg OIT was profiled using peripheral blood mononuclear cell (PBMC) samples obtained at baseline and after 3 and 8 months of OIT. We identified 467 differentially expressed genes (DEGs) after 3 or 8 months of egg OIT. At 8 months, 86% of the DEGs were downregulated and played a role in the signaling of TREM1, IL-6, and IL-17. In correlation analyses, Gal d 1–4-specific IgG4 antibodies associated positively with DEGs playing a role in pathogen recognition and antigen presentation and negatively with DEGs playing a role in the signaling of IL-10, IL-6, and IL-17. Desensitized and partially desensitized patients had differences in their antibody responses, and although most of the transcriptomic changes were shared, both groups had also specific patterns, which suggest slower changes in partially desensitized and activation of NK cells in the desensitized group. OIT for egg allergy in children inhibits inflammation and activates innate immune responses regardless of the clinical outcome at 8 months. Changes in gene expression patterns first appear as posttranslational protein modifications, followed by more sustained epigenetic gene regulatory functions related to successful desensitization.
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| 39. |
- Karra, L, et al.
(författare)
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CD300a: A New Player in Atopic Dermatitis?
- 2017
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Ingår i: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. - : Elsevier BV. - 0091-6749. ; 139:2, s. AB238-AB238
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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- Martens, A, et al.
(författare)
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An optimized, robust and reproducible protocol to generate well-differentiated primary nasal epithelial models from extremely premature infants
- 2019
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 20069-
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Tidskriftsartikel (refereegranskat)abstract
- Extremely premature infants are prone to severe respiratory infections, and the mechanisms underlying this exceptional susceptibility are largely unknown. Nasal epithelial cells (NEC) represent the first-line of defense and adult-derived ALI cell culture models show promising results in mimicking in vivo physiology. Therefore, the aim of this study was to develop a robust and reliable protocol for generating well-differentiated cell culture models from NECs of extremely premature infants. Nasal brushing was performed in 13 extremely premature infants at term corrected age and in 11 healthy adult controls to obtain NECs for differentiation at air-liquid interface (ALI). Differentiation was verified using imaging and functional analysis. Successful isolation and differentiation was achieved for 5 (38.5%) preterm and 5 (45.5%) adult samples. Preterm and adult ALI-cultures both showed well-differentiated morphology and ciliary function, however, preterm cultures required significantly longer cultivation times for acquiring full differentiation (44 ± 3.92 vs. 23 ± 1.83 days; p < 0.0001). Moreover, we observed that recent respiratory support may impair successful NECs isolation. Herewithin, we describe a safe, reliable and reproducible method to generate well-differentiated ALI-models from NECs of extremely premature infants. These models provide a valuable foundation for further studies regarding immunological and inflammatory responses and respiratory disorders in extremely premature infants.
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- Ndika, J, et al.
(författare)
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Epigenetic Differences in Long Non-coding RNA Expression in Finnish and Russian Karelia Teenagers With Contrasting Risk of Allergy and Asthma
- 2022
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Ingår i: Frontiers in allergy. - : Frontiers Media SA. - 2673-6101. ; 3, s. 878862-
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Tidskriftsartikel (refereegranskat)abstract
- Previously, we investigated skin microbiota and blood cell gene expression in Finnish and Russian teenagers with contrasting incidence of allergic conditions. The microbiota and transcriptomic signatures were distinctly different, with high Acinetobacter abundance and suppression of genes regulating innate immune response in healthy subjects.ObjectiveHere, we investigated long non-coding RNA (lncRNA) expression profiles of blood mononuclear cells (PBMC) from healthy and allergic subjects, to identify lncRNAs that act at the interphase of microbiome-mediated immune homeostasis in allergy/asthma.MethodsGenome-wide co-expression network analyses of blood cell lncRNA/mRNA expression was integrated with skin microbiota profiles of Finnish (69) and Russian (75) subjects. Selected lncRNAs were validated by stimulation of cohort-derived PBMCs and a macrophage cell model with birch pollen allergen (Betv1) or lipopolysaccharide, respectively.ResultsFinnish and Russian PBMCs were differentiated by 3,818 lncRNA transcripts. In the Finnish subjects with high prevalence of allergy and asthma, a subset of 37 downregulated lncRNAs (including, FAM155A-IT1 and LOC400958) were identified. They were part of a co-expression network with 20 genes known to be related to asthma and allergic rhinitis (R > 0.95). Incidentally, all these 20 genes were also components of pathways corresponding to cellular response to bacterium. The Finnish and Russian samples were also differentiated by the abundance of 176 bacterial OTU (operational taxonomic units). The subset of 37 lncRNAs, associated with allergy, was most correlated with the abundance of Acinetobacter (R > +0.5), Jeotgalicoccus (R > +0.5), Corynebacterium (R < −0.5) and Micrococcus (R < −0.5).ConclusionIn Finnish and Russian teenagers with contrasting allergy and asthma prevalence, epigenetic differences in lncRNA expression appear to be important components of the underlying microbiota-immune interactions. Unraveling the functions of the 37 differing lncRNAs may be the key to understanding microbiome-immune crosstalk, and to develop clinically relevant biomarkers.
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