NDLI: ICOS-expressing CD4 T cells induced via TLR4 in the nasal mucosa are capable of inhibiting experimental allergic asthma.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Tsuchiya, Kimitake Jo, Taisuke Nakada, Emily Allard-Coutu, Alexandra Rioux, Clément R. Hirota, Nobuaki Maghni, Karim Shalaby, Karim H. Qureshi, Salman T. Martin, James G.
Description	Country affiliation: Canada Author Affiliation: Shalaby KH ( Meakins-Christie Laboratories, Department of Medicine, McGill University and McGill University Health Centre Research Institute, Montreal, Quebec H2X 2P2, Canada.)
Abstract	Modulation of adaptive immune responses via the innate immune pattern recognition receptors, such as the TLRs, is an emerging strategy for vaccine development. We investigated whether nasal rather than intrapulmonary application of Protollin, a mucosal adjuvant composed of TLR2 and TLR4 ligands, is sufficient to elicit protection against murine allergic lower airway disease. Wild-type, Tlr2(-/-), or Tlr4(-/-) BALB/c mice were sensitized to a birch pollen allergen extract (BPEx), then received either intranasal or intrapulmonary administrations of Protollin or Protollin admixed with BPEx, followed by consecutive daily BPEx challenges. Nasal application of Protollin or Protollin admixed with BPEx was sufficient to inhibit allergic lower airway disease with minimal collateral lung inflammation. Inhibition was dependent on TLR4 and was associated with the induction of ICOS in cells of the nasal mucosa and on both CD4+Foxp3+ and CD4+Foxp3- T cells of the draining lymph nodes (LNs), as well as their recruitment to the lungs. Adoptive transfer of cervical LN CD4+ICOS+, but not CD4+ICOS-, cells inhibited BPEx-induced airway hyperresponsiveness and bronchoalveolar lavage eosinophilia. Thus, our data indicate that expansion of resident ICOS-expressing CD4+ T cells of the cervical LNs by nasal mucosal TLR4 stimulation may inhibit the development of allergic lower airway disease in mice.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	6
Volume Number	189
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2012-09-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Asthma Prevention & Control Cd4-positive T-lymphocytes Immunology Inducible T-cell Co-stimulator Protein Biosynthesis Lymphocyte Activation Nasal Mucosa Toll-like Receptor 4 Physiology Animals Drug Therapy Betula Metabolism Transplantation Mice Mice, Inbred Balb C Mice, Knockout Pathology Pollen Respiratory Hypersensitivity Deficiency Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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