The TLR4-TRIF pathway can protect against the development of experimental allergic asthma

Autor: Kimitake Tsuchiya, Saba Al Heialy, Karim H. Shalaby, Salman T. Qureshi, Woong-Kyung Suh, James G. Martin, Toby K. McGovern, Paul-André Risse, Soroor Farahnak
Rok vydání: 2016
Předmět:
0301 basic medicine
CD4-Positive T-Lymphocytes
Lipopolysaccharides
Adoptive cell transfer
Time Factors
Lymphocyte Activation
0302 clinical medicine
Interferon
Immunology and Allergy
Medicine
Lung
Betula
Mice
Knockout
Mice
Inbred BALB C
FOXP3
Signal transducing adaptor protein
Adoptive Transfer
3. Good health
Chemotaxis
Leukocyte
Cysteine Endopeptidases
Drug Combinations
medicine.anatomical_structure
Phenotype
Pollen
Female
Bronchial Hyperreactivity
medicine.drug
Signal Transduction
T cell
Bronchoconstriction
Immunology
Inducible T-Cell Co-Stimulator Protein
03 medical and health sciences
Animals
Genetic Predisposition to Disease
Cell Proliferation
business.industry
Rhinitis
Allergic
Seasonal
Original Articles
Antigens
Plant
Asthma
Mice
Inbred C57BL
Toll-Like Receptor 4
TLR2
Adaptor Proteins
Vesicular Transport
Disease Models
Animal
030104 developmental biology
TRIF
Myeloid Differentiation Factor 88
TLR4
business
030215 immunology
Zdroj: Immunology. 152(1)
ISSN: 1365-2567
Popis: The Toll-like Receptor (TLR) adaptor proteins Myeloid Differentiating Factor 88 (MyD88) and Toll, interleukin-1 Receptor and Resistance protein (TIR) domain-containing adaptor inducing interferon-β (TRIF) comprise the two principal limbs of the TLR signaling network. We studied the role of these adaptors in the TLR4-dependent inhibition of allergic airway disease and induction of CD4+ICOS+ T cells by nasal application of Protollin™, a mucosal adjuvant composed of TLR2 and 4 agonists. Wild-type (wt), Trif -/- or Myd88 -/- mice were sensitized to birch pollen extract (BPEx), then received intranasal Protollin followed by consecutive BPEx challenges. Protollin's protection against allergic airway disease was TRIF-dependent and MyD88-independent. TRIF-deficiency diminished the CD4+ICOS+ T cell subsets in the lymph nodes draining the nasal mucosa, as well as their recruitment to the lungs. Overall, TRIF-deficiency reduced the proportion of cervical lymph node and lung CD4+ICOS+Foxp3- cells, in particular. Adoptive transfer of cervical lymph node cells supported a role for Protollin-induced CD4+ICOS+ cells in the TRIF-dependent inhibition of AHR. Thus, our data demonstrate that stimulation of the TLR4-TRIF pathway can protect against the development of allergic airway disease and that a TRIF-dependent adjuvant effect on CD4+ICOS+ T cell responses may be a contributing mechanism. This article is protected by copyright. All rights reserved.
Databáze: OpenAIRE
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