MyD88 modulates eosinophil and neutrophil recruitment as well as IL-17A production during allergic inflammation.
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.
Université Paris Descartes, Paris 75015, France; CNRS UMR 8147, Necker Hospital, Paris 75015, France.
Linh
L
Pham Van
Université Paris Descartes, Paris 75015, France; CNRS UMR 8147, Necker Hospital, Paris 75015, France.
Nathalie
N
Germaud
Université Paris Descartes, Paris 75015, France; CNRS UMR 8147, Necker Hospital, Paris 75015, France.
Abdulraouf
A
Ramadan
Université Paris Descartes, Paris 75015, France; CNRS UMR 8147, Necker Hospital, Paris 75015, France; INSERM U1016, Institut Cochin, Paris, France; CNRS UMR8104, Paris, France; Center of Excellence, INFLAMEX, France. Electronic address: nathalie.thieblemont@inserm.fr.
Nathalie
N
Thieblemont
D000818:Animals; D002465:Cell Movement / Q000235:genetics; D002478:Cells, Cultured; D004804:Eosinophils / Q000276:immunology*; D006967:Hypersensitivity / Q000276:immunology*; D020381:Interleukin-17 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism*; D009504:Neutrophils / Q000276:immunology*; D011014:Pneumonia / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D020381:Interleukin-17; D053594:Myeloid Differentiation Factor 88
Allergic asthma; Eosinophils; Inflammation; MyD88; Neutrophils; Th17 cells