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Sublingual allergen immunotherapy prevents house dust mite inhalant type 2 immunity through dendritic cell-mediated induction of Foxp3+ regulatory T cells

(2024) MUCOSAL IMMUNOLOGY. 17(4). p.618-632
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Abstract
Sublingual allergen immunotherapy (SLIT) is an emerging treatment option for allergic asthma and a potential disease-modifying strategy for asthma prevention. The key cellular events leading to such long-term tolerance remain to be fully elucidated. We administered prophylactic SLIT in a mouse model of house dust mite (HDM)-driven allergic asthma. HDM extract was sublingually administered over 3 weeks followed by intratracheal sensitization and intranasal challenges with HDM. Prophylactic SLIT prevented allergic airway inflammation and hyperreactivity with a low lab-to-lab variation. The HDM-specific T helper (Th)2 (cluster of differentiation 4 Th) response was shifted by SLIT toward a regulatory and Th17 response in the lung and mediastinal lymph node. By using Derp1-specific cluster of differentiation 4+ T cells (1-DER), we found that SLIT blocked 1-DER T cell recruitment to the mediastinal lymph node and dampened IL-4 secretion following intratracheal HDM sensitization. Sublingually administered Derp1 protein activated 1-DER T cells in the cervical lymph node via chemokine receptor7+ migratory dendritic cells (DC). DCs migrating from the oral submucosa to the cervical lymph node after SLIT-induced Foxp3+ regulatory T cells. When mice were sensitized with HDM, prior prophylactic SLIT increased Derp1 specific regulatory T cells (Tregs) and lowered Th2 recruitment in the lung. By using Foxp3-diphtheria toxin receptor mice, Tregs were found to contribute to the immunoregulatory prophylactic effect of SLIT on type 2 immunity. These findings in a mouse model suggest that DC-mediated functional Treg induction in oral mucosa draining lymph nodes is one of the driving mechanisms behind the disease-modifying effect of prophylactic SLIT.
Keywords
RANDOMIZED CONTROLLED-TRIAL, GRASS-POLLEN IMMUNOTHERAPY, DOUBLE-BLIND, CLINICAL-EFFICACY, IMMUNOGLOBULIN-A, IN-VIVO, TABLET, ASTHMA, RESPONSES, INFLAMMATION

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MLA
Van Der Borght, Katrien, et al. “Sublingual Allergen Immunotherapy Prevents House Dust Mite Inhalant Type 2 Immunity through Dendritic Cell-Mediated Induction of Foxp3+ Regulatory T Cells.” MUCOSAL IMMUNOLOGY, vol. 17, no. 4, 2024, pp. 618–32, doi:10.1016/j.mucimm.2024.03.012.
APA
Van Der Borght, K., Brimnes, J., Haspeslagh, E., Brand, S., Neyt, K., Gupta, S., … Lambrecht, B. (2024). Sublingual allergen immunotherapy prevents house dust mite inhalant type 2 immunity through dendritic cell-mediated induction of Foxp3+ regulatory T cells. MUCOSAL IMMUNOLOGY, 17(4), 618–632. https://doi.org/10.1016/j.mucimm.2024.03.012
Chicago author-date
Van Der Borght, Katrien, Jens Brimnes, Eline Haspeslagh, Stephanie Brand, Katrijn Neyt, Shashank Gupta, Niels Peter Hell Knudsen, Hamida Hammad, Peter S. Andersen, and Bart Lambrecht. 2024. “Sublingual Allergen Immunotherapy Prevents House Dust Mite Inhalant Type 2 Immunity through Dendritic Cell-Mediated Induction of Foxp3+ Regulatory T Cells.” MUCOSAL IMMUNOLOGY 17 (4): 618–32. https://doi.org/10.1016/j.mucimm.2024.03.012.
Chicago author-date (all authors)
Van Der Borght, Katrien, Jens Brimnes, Eline Haspeslagh, Stephanie Brand, Katrijn Neyt, Shashank Gupta, Niels Peter Hell Knudsen, Hamida Hammad, Peter S. Andersen, and Bart Lambrecht. 2024. “Sublingual Allergen Immunotherapy Prevents House Dust Mite Inhalant Type 2 Immunity through Dendritic Cell-Mediated Induction of Foxp3+ Regulatory T Cells.” MUCOSAL IMMUNOLOGY 17 (4): 618–632. doi:10.1016/j.mucimm.2024.03.012.
Vancouver
1.
Van Der Borght K, Brimnes J, Haspeslagh E, Brand S, Neyt K, Gupta S, et al. Sublingual allergen immunotherapy prevents house dust mite inhalant type 2 immunity through dendritic cell-mediated induction of Foxp3+ regulatory T cells. MUCOSAL IMMUNOLOGY. 2024;17(4):618–32.
IEEE
[1]
K. Van Der Borght et al., “Sublingual allergen immunotherapy prevents house dust mite inhalant type 2 immunity through dendritic cell-mediated induction of Foxp3+ regulatory T cells,” MUCOSAL IMMUNOLOGY, vol. 17, no. 4, pp. 618–632, 2024.
@article{01HYJQSY2N9WQDYHENGDQ69TN6,
  abstract     = {{Sublingual allergen immunotherapy (SLIT) is an emerging treatment option for allergic asthma and a potential disease-modifying strategy for asthma prevention. The key cellular events leading to such long-term tolerance remain to be fully elucidated. We administered prophylactic SLIT in a mouse model of house dust mite (HDM)-driven allergic asthma. HDM extract was sublingually administered over 3 weeks followed by intratracheal sensitization and intranasal challenges with HDM. Prophylactic SLIT prevented allergic airway inflammation and hyperreactivity with a low lab-to-lab variation. The HDM-specific T helper (Th)2 (cluster of differentiation 4 Th) response was shifted by SLIT toward a regulatory and Th17 response in the lung and mediastinal lymph node. By using Derp1-specific cluster of differentiation 4+ T cells (1-DER), we found that SLIT blocked 1-DER T cell recruitment to the mediastinal lymph node and dampened IL-4 secretion following intratracheal HDM sensitization. Sublingually administered Derp1 protein activated 1-DER T cells in the cervical lymph node via chemokine receptor7+ migratory dendritic cells (DC). DCs migrating from the oral submucosa to the cervical lymph node after SLIT-induced Foxp3+ regulatory T cells. When mice were sensitized with HDM, prior prophylactic SLIT increased Derp1 specific regulatory T cells (Tregs) and lowered Th2 recruitment in the lung. By using Foxp3-diphtheria toxin receptor mice, Tregs were found to contribute to the immunoregulatory prophylactic effect of SLIT on type 2 immunity. These findings in a mouse model suggest that DC-mediated functional Treg induction in oral mucosa draining lymph nodes is one of the driving mechanisms behind the disease-modifying effect of prophylactic SLIT.}},
  author       = {{Van Der Borght, Katrien and Brimnes, Jens and Haspeslagh, Eline and Brand, Stephanie and Neyt, Katrijn and Gupta, Shashank and Knudsen, Niels Peter Hell and Hammad, Hamida and Andersen, Peter S. and Lambrecht, Bart}},
  issn         = {{1933-0219}},
  journal      = {{MUCOSAL IMMUNOLOGY}},
  keywords     = {{RANDOMIZED CONTROLLED-TRIAL,GRASS-POLLEN IMMUNOTHERAPY,DOUBLE-BLIND,CLINICAL-EFFICACY,IMMUNOGLOBULIN-A,IN-VIVO,TABLET,ASTHMA,RESPONSES,INFLAMMATION}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{618--632}},
  title        = {{Sublingual allergen immunotherapy prevents house dust mite inhalant type 2 immunity through dendritic cell-mediated induction of Foxp3+ regulatory T cells}},
  url          = {{http://doi.org/10.1016/j.mucimm.2024.03.012}},
  volume       = {{17}},
  year         = {{2024}},
}

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