Research paperMyD88 modulates eosinophil and neutrophil recruitment as well as IL-17A production during allergic inflammation

- The lack of MyD88 offers a partial protection from allergic disease.
- MyD88 is critical for orchestrating eosinophil and neutrophil recruitment.
- CD4+ T cells from MyD88−/− mice exhibited an impaired IL-17A production.
- The number of Th17-associated effectors in LN from MyD88−/− mice is decreased.

The contribution of dysregulated innate immune responses to the pathogenesis of allergic disease remains largely unknown. Herein, we addressed the role of Toll-like receptor signaling in airway inflammation by studying mice rendered deficient for the myeloid differentiation factor 88 (MyD88−/−) which results in concurrent deficiencies in TLR and IL-1R1 signaling pathways. We show that the lack of MyD88 offers a partial protection from allergic disease evidenced by reduced airway eosinophilia and production of the Th17-associated effector cytokine IL-17A. By contrast, airway hyperreactivity and Th2 cytokine production, the cardinal features of allergic disease, remained unchanged. We found that the impaired IL-17A production in MyD88−/− mice was associated with defective CD4+ T cells, which failed to respond to IL-23 stimulation. The total number of Th17-associated effectors in lymph nodes was likewise decreased. Taken together, our results demonstrate that MyD88-dependent mechanisms are critical for orchestrating lung inflammatory responses, in terms of IL-17A production, as well as eosinophil and neutrophil recruitment.