Journal
JCI INSIGHT
Volume 7, Issue 4, Pages -Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/jci.insight.150251
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Funding
- NIH, the NIEHS [ZIA ES102025-09]
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The type of adjuvant used during allergic sensitization has a profound effect on the nature and longevity of the pulmonary inflammation triggered by subsequent reexposure to the same allergen.
The intensity and longevity of inflammatory responses to inhaled allergens is determined largely by the balance between effector and regulatory immune responses, but the mechanisms that determine the relative magnitudes of these opposing forces remain poorly understood. We have found that the type of adjuvant used during allergic sensitization has a profound effect on both the nature and longevity of the pulmonary inflammation triggered by subsequent reexposure to that same provoking allergen. TLR ligand adjuvants and house dust extracts primed immune responses characterized by a mixed neutrophilic and eosinophilic inflammation that was suppressed by multiple daily allergen challenges. During TLR ligand-mediated allergic sensitization, mice displayed transient airway neutrophilia, which triggered the release of TGF-beta into the airway. This neutrophil-dependent production of TGF-beta during sensitization had a delayed, suppressive effect on eosinophilic responses to subsequent allergen challenge. Neutrophil depletion during sensitization did not affect numbers of Foxp3(+) Tregs but increased proportions of Gata3(+)CD4(+) T cells, which, upon their transfer to recipient mice, triggered stronger eosinophilic inflammation. Thus, a neutrophil/TGF-beta axis acts during TLR-mediated allergic sensitization to fine-tune the phenotype of developing allergen-specific CD4(+) T cells and limit their pathogenicity, suggesting a novel immunotherapeutic approach to control eosinophilia in asthma.
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