Tolerogenic T cells, Th1/Th17 cytokines and TLR2/TLR4 expressing dendritic cells predominate the microenvironment within distinct oral mucosal sites

Allam, Jean‐Pierre; Duan, Yong‐Gang; Winter, Jochen; Stojanovski, Gligor; Fronhoffs, Florian; Wenghoefer, Matthias; Bieber, Thomas; Peng, Wenming; Novak, Natalija

doi:10.1111/j.1398-9995.2010.02510.x

Cited by 58 publications

(39 citation statements)

References 27 publications

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“…Thereby, T cells producing tolerogenic cytokine IL-10 with inhibitory capacity could be demonstrated in oral mucosal tissue of BALB/c mice [19]. In line with this study, T cells producing tolerogenic cytokines TGF-b1 and IL-10 could also be detected in different regions of oral human mucosal tissue [18 ]. Beyond the presence of regulatory T cells in mice and human oral mucosal tissue, both studies [18 ,19] could demonstrate the presence of Th1 cells producing interferon (IFN)-g. In humans, oral mucosal tissue Th2-cytokine producing T cells could not be found, whereas IL-4 producing T cells could be detected in oral mucosal tissue of BALB/c mice [18 ,19].…”

Section: Recent Findingssupporting

confidence: 85%

Local immunological mechanisms of sublingual immunotherapy

Allam

Novak

2011

Current Opinion in Allergy &Amp; Clinical Immunology

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Section: Recent Findingssupporting

confidence: 85%

Local immunological mechanisms of sublingual immunotherapy

Allam

Novak

2011

Current Opinion in Allergy &Amp; Clinical Immunology

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“…5 In contrast, tolerogenic DCs have been detected at mucosal surfaces, such as within the oral mucosa, and have proved critical to establish clinical tolerance after sublingual AIT through the induction of T H 1 and Treg cell responses in draining cervical lymph nodes. [24][25][26][27][28] Collectively, these observations support the hypothesis that the polarization of immune responses could be assessed at the level of DCs with immediate application to the follow-up of AIT.…”

Section: Discussionsupporting

confidence: 50%

A regulatory dendritic cell signature correlates with the clinical efficacy of allergen-specific sublingual immunotherapy

Zimmer¹,

Bouley²,

Mignon³

et al. 2012

Journal of Allergy and Clinical Immunology

138

159

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“…Although the protective mechanisms for this strategy remain elusive, they likely involve priming of CD4 + T cells by mucosal APCs, among which DCs, Langerhans cells, and macrophages have each been implicated. 174,175 Dust mite allergen provides an attractive target for this therapeutic modality, given the high prevalence of sensitization among allergic asthmatic patients. Indeed, the efficacy of dust mite SLIT in reducing rhinitis symptoms was recently established in an environmental exposure chamber study.…”

Section: Future Directions and Clinical Implicationsmentioning

confidence: 99%

Pathogenic CD4 + T cells in patients with asthma

Muehling

Lawrence

Woodfolk

2017

Journal of Allergy and Clinical Immunology

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Asthma encompasses a variety of clinical phenotypes that involve distinct T cell–driven inflammatory processes. Improved understanding of human T-cell biology and the influence of innate cytokines on T-cell responses at the epithelial barrier has led to new asthma paradigms. This review captures recent knowledge on pathogenic CD4+ T cells in asthmatic patients by drawing on observations in mouse models and human disease. In patients with allergic asthma, TH2 cells promote IgE-mediated sensitization, airway hyperreactivity, and eosinophilia. Here we discuss recent discoveries in the myriad molecular pathways that govern the induction of TH2 differentiation and the critical role of GATA-3 in this process. We elaborate on how cross-talk between epithelial cells, dendritic cells, and innate lymphoid cells translates to T-cell outcomes, with an emphasis on the actions of thymic stromal lymphopoietin, IL-25, and IL-33 at the epithelial barrier. New concepts on how T-cell skewing and epitope specificity are shaped by multiple environmental cues integrated by dendritic cell “hubs” are discussed. We also describe advances in understanding the origins of atypical TH2 cells in asthmatic patients, the role of TH1 cells and other non-TH2 types in asthmatic patients, and the features of T-cell pathogenicity at the single-cell level. Progress in technologies that enable highly multiplexed profiling of markers within a single cell promise to overcome barriers to T-cell discovery in human asthmatic patients that could transform our understanding of disease. These developments, along with novel T cell–based therapies, position us to expand the assortment of molecular targets that could facilitate personalized treatments.

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Tolerogenic T cells, Th1/Th17 cytokines and TLR2/TLR4 expressing dendritic cells predominate the microenvironment within distinct oral mucosal sites

Abstract: From this data, we conclude that (i) VBR and SLR represent a protolerogenic micromilieu, (ii) both regions form a Th1 cytokine-predominated microenvironment, but also express mRNA for Th17 cytokines and (iii) TLRs detectable in VBR and SLR might serve as a target structures for adjuvants.

Cited by 58 publications

References 27 publications

Local immunological mechanisms of sublingual immunotherapy

Local immunological mechanisms of sublingual immunotherapy

A regulatory dendritic cell signature correlates with the clinical efficacy of allergen-specific sublingual immunotherapy

Pathogenic CD4 + T cells in patients with asthma

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