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IL ‐4 receptor α blockade prevents sensitization and alters acute and long‐lasting effects of allergen‐specific immunotherapy of murine allergic asthma
Author(s) -
Russkamp D.,
AguilarPimentel A.,
Alessandrini F.,
GailusDurner V.,
Fuchs H.,
Ohnmacht C.,
Chaker A.,
Angelis M. H.,
Ollert M.,
SchmidtWeber C. B.,
Blank S.
Publication year - 2019
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.13759
Subject(s) - sensitization , immunoglobulin e , medicine , immunology , allergy , blockade , allergen , immunotherapy , asthma , cytokine , antibody , receptor , immune system
Abstract Background Allergen‐specific immunotherapy ( AIT ) is the only causal treatment for allergy. However, success rates vary depending on the type of allergy and disease background of the patient. Hence, strategies targeting an increased therapeutic efficacy are urgently needed. Here, the effects of blockade of IL ‐4 and IL ‐13 signaling on different phases of AIT were addressed. Methods The impact of the recombinantly produced IL ‐4 and IL ‐13 antagonist IL ‐4 mutein ( IL ‐4M) on allergic sensitization and AIT outcome in experimental allergic asthma were analyzed in a murine model. The effects of IL ‐4M administration were assessed prior/during sensitization, immediately after AIT under allergen challenge, and two weeks post‐treatment. Results Intervention with IL ‐4M prior/during sensitization led to strong induction of IgG1, IgG2a, IgG2b, and IgG3, decrease of specific and total IgE, as well as of IL ‐5 in serum. Similar effects on the serum immunoglobulin levels were observed immediately after IL 4M‐supplemented AIT during allergen challenge. Additionally, IL 4M markedly suppressed type‐2 cytokine secretion of splenocytes beyond the effect of AIT alone. These effects were equaled to those of AIT alone two weeks post‐treatment. Intriguingly, here, IL ‐4M induced a sustained decrease of Th2‐biased Tregs ( ST 2 + FOXP 3 + GATA 3 intermediate ). Conclusions IL ‐4 and IL ‐13 blockade during experimental AIT demonstrates beneficial effects on immunological key parameters such as immunoglobulin and cytokine secretion immediately after AIT . Although two weeks later these effects were dropped to those of AIT alone, the number of potentially disease‐triggering Th2‐biased Tregs was further significantly decreased by IL ‐4M treatment. Hence, IL ‐4/ IL 13‐targeting therapies prime the immune memory in therapy success‐favoring manner.