TY - JOUR
T1 - T cell-independent mechanisms associated with neutrophil extracellular trap formation and selective autophagy in IL-17A-mediated epidermal hyperplasia
AU - Suzuki, Erika
AU - Maverakis, Emanual
AU - Sarin, Ritu
AU - Bouchareychas, Laura
AU - Kuchroo, Vijay K.
AU - Nestle, Frank O.
AU - Adamopoulos, Iannis E.
N1 - Publisher Copyright:
© 2016 by The American Association of Immunologists, Inc. All rights reserved.
PY - 2016/12/1
Y1 - 2016/12/1
N2 - IL-17A has been strongly associated with epidermal hyperplasia in many cutaneous disorders. However, because IL-17A is mainly produced by ab and ≥mma;δT cells in response to IL-23, the role of T cells and IL-23 has overshadowed any IL-17A-independent actions. In this article, we report that IL-17A gene transfer induces epidermal hyperplasia in Il23r-/-Rag1-/- and Tcrd-deficient mice, which can be prevented by neutrophil depletion. Moreover, adoptive transfer of CD11b+Gr-1hi cells, after IL-17A gene transfer, was sufficient to phenocopy the disease. We further show that the IL-17A-induced pathology was prevented in transgenic mice with impaired neutrophil extracellular trap formation and/or neutrophils with conditional deletion of the master regulator of selective autophagy, Wdfy3. Our data demonstrate a novel T cell-independent mechanism that is associated with neutrophil extracellular trap formation and selective autophagy in IL-17A-mediated epidermal hyperplasia.
AB - IL-17A has been strongly associated with epidermal hyperplasia in many cutaneous disorders. However, because IL-17A is mainly produced by ab and ≥mma;δT cells in response to IL-23, the role of T cells and IL-23 has overshadowed any IL-17A-independent actions. In this article, we report that IL-17A gene transfer induces epidermal hyperplasia in Il23r-/-Rag1-/- and Tcrd-deficient mice, which can be prevented by neutrophil depletion. Moreover, adoptive transfer of CD11b+Gr-1hi cells, after IL-17A gene transfer, was sufficient to phenocopy the disease. We further show that the IL-17A-induced pathology was prevented in transgenic mice with impaired neutrophil extracellular trap formation and/or neutrophils with conditional deletion of the master regulator of selective autophagy, Wdfy3. Our data demonstrate a novel T cell-independent mechanism that is associated with neutrophil extracellular trap formation and selective autophagy in IL-17A-mediated epidermal hyperplasia.
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U2 - 10.4049/jimmunol.1600383
DO - 10.4049/jimmunol.1600383
M3 - Article
C2 - 27798153
AN - SCOPUS:84996490557
SN - 0022-1767
VL - 197
SP - 4403
EP - 4412
JO - Journal of Immunology
JF - Journal of Immunology
IS - 11
ER -