Epigenetic and Transcriptional Regulation in the Induction, Maintenance, Heterogeneity, and Recall-Response of Effector and Memory Th2 Cells

Onodera, Atsushi; Kokubo, Kota; Nakayama, Toshinori

doi:10.3389/fimmu.2018.02929

Cited by 25 publications

(21 citation statements)

References 110 publications

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“…Allergen-specific Th2 cells orchestrate allergic airway inflammation by producing type 2 cytokines, including IL-4, IL-5, and IL-13, which drive eosinophilic inflammation, mucus metaplasia, and airway hyperresponsiveness ( Lambrecht et al, 2019 ; Walker and McKenzie, 2018 ). In addition, Th2 cells can give rise to long-lived memory Th2 cells that maintain allergen-specific immunity ( Hondowicz et al, 2016 ; Onodera et al, 2018 ). Consequently, memory Th2 cells represent an attractive therapeutic target in allergic asthma, but our knowledge of memory Th2 biology in vivo remains limited.…”

Section: Introductionmentioning

confidence: 99%

Distinct functions of tissue-resident and circulating memory Th2 cells in allergic airway disease

Rahimi

Nepal

Çetinbaş

et al. 2020

Journal of Experimental Medicine

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Memory CD4+ T helper type 2 (Th2) cells drive allergic asthma, yet the mechanisms whereby tissue-resident memory Th2 (Th2 Trm) cells and circulating memory Th2 cells collaborate in vivo remain unclear. Using a house dust mite (HDM) model of allergic asthma and parabiosis, we demonstrate that Th2 Trm cells and circulating memory Th2 cells perform nonredundant functions. Upon HDM rechallenge, circulating memory Th2 cells trafficked into the lung parenchyma and ignited perivascular inflammation to promote eosinophil and CD4+ T cell recruitment. In contrast, Th2 Trm cells proliferated near airways and induced mucus metaplasia, airway hyperresponsiveness, and airway eosinophil activation. Transcriptional analysis revealed that Th2 Trm cells and circulating memory Th2 cells share a core Th2 gene signature but also exhibit distinct transcriptional profiles. Th2 Trm cells express a tissue-adaptation signature, including genes involved in regulating and interacting with extracellular matrix. Our findings demonstrate that Th2 Trm cells and circulating memory Th2 cells are functionally and transcriptionally distinct subsets with unique roles in promoting allergic airway disease.

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Section: Introductionmentioning

confidence: 99%

Distinct functions of tissue-resident and circulating memory Th2 cells in allergic airway disease

Rahimi

Nepal

Çetinbaş

et al. 2020

Journal of Experimental Medicine

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“…Antigen-specific Th2 cells cause allergic diseases, such as asthma, rhinitis, and atopic dermatitis, by producing Th2 cytokines (IL-4, IL-5, and IL-13). Antigen-specific Th2 cells generally exist as memory Th2 cells in vivo , and become activated and mediate allergic inflammation immediately after exposure to specific antigens [ 19 – 21 ]. We previously reported the involvement of antigen-specific Th2 cells in rhinitis, using a mouse model, and found that the nasal activation of antigen-specific Th2 cells induced rhinitis symptoms even in the absence of IgE, mast cells, and basophils [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Th2 cells and macrophages cooperatively induce allergic inflammation through histamine signaling

Iwasaki¹,

Shimizu²,

Oikawa³

et al. 2021

PLoS ONE

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Histamine, which is mainly produced by mast cells and basophils, participates in various allergic symptoms, and some studies have reported that macrophages also produce histamine. Moreover, recent studies have revealed that macrophages, especially alternatively activated macrophages (M2) induced by T helper 2 (Th2) cytokines, such as interleukin (IL)-4 and IL-13, participate in the pathogenesis of allergic diseases. The major source of Th2 cytokines is antigen-specific Th2 cells. To elucidate the relationship between histamine, macrophages, and Th2 cells in allergic inflammation, we established a macrophage-Th2 cell co-culture model in vitro and an antigen-specific Th2 cell transfer mouse model of rhinitis. In vitro analyses indicated that macrophages produce histamine by interacting with antigen-specific Th2 cells through the antigen. Furthermore, Th2 cells and macrophages cooperatively elicited rhinitis in the mouse model. We determined that histamine induces Th2- and macrophage-elicited sneezing responses through H1 receptor signaling, whereas it induces nasal eosinophil infiltrations through H4 receptor signaling. Collectively, these results indicate a novel histamine production mechanism by macrophages, in which Th2 cells and macrophages cooperatively induce nasal allergic inflammation through histamine signaling.

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“…However, natural substances, such as polyphenols, that can interfere with phase I and/or II enzymes and/or with enteric P-glycoprotein enhance its plasma levels in rats ∼6-fold (73). Finally, among the three compounds tested in our investigation, cannabidiol is the only ingredient that has been studied in dogs, where its detected oral bioavailability ranged from 13 to 19% of the administered dose (74,75). Therefore, despite our study being performed in vitro, these previously reported findings suggest that our results could be considered valid with respect to a nutraceutical approach to treating canine AD.…”

Section: Discussionmentioning

confidence: 81%

Polyphenols and Cannabidiol Modulate Transcriptional Regulation of Th1/Th2 Inflammatory Genes Related to Canine Atopic Dermatitis

Massimini¹,

Vedove²,

Bachetti³

et al. 2021

Front. Vet. Sci.

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Canine atopic dermatitis (AD) is a multifactorial allergic disease associated with immune and abnormal skin barrier dysfunction and it is one of the primary causes of pruritus. Using a novel in vitro model of AD, here we tried to revert the alteration of transcriptional regulation of AD canine key genes testing a nutraceutical mixture containing flavonoids, stilbene, and cannabinoids, which are already well-known for their applications within dermatology diseases. The nutraceutical mixture induced in inflamed cells a significant downregulation (p < 0.05) of the gene expression of ccl2, ccl17, and tslp in keratinocytes and of ccl2, ccl17, and il31ra in monocytes. Consistent with the observed alterations of tslp, ccl2, ccl17, and il31ra messenger RNA (mRNA) levels, a significant increase (p < 0.05) of DNA methylation at specific CpG sites on the gene regulatory regions was found. These results lay the foundation for the use of these natural bioactives in veterinary medicine and provide a model for deeper understanding of their mechanisms of action, with potential translation to human research.

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Epigenetic and Transcriptional Regulation in the Induction, Maintenance, Heterogeneity, and Recall-Response of Effector and Memory Th2 Cells

Cited by 25 publications

References 110 publications

Distinct functions of tissue-resident and circulating memory Th2 cells in allergic airway disease

Distinct functions of tissue-resident and circulating memory Th2 cells in allergic airway disease

Th2 cells and macrophages cooperatively induce allergic inflammation through histamine signaling

Polyphenols and Cannabidiol Modulate Transcriptional Regulation of Th1/Th2 Inflammatory Genes Related to Canine Atopic Dermatitis

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