In:
The Journal of Immunology, The American Association of Immunologists, Vol. 198, No. 1_Supplement ( 2017-05-01), p. 61.2-61.2
Abstract:
IL-17C is highly expressed in psoriasis skin and is thought to promote inflammation by binding IL-17RA and IL-17RE. Keratinocyte-overexpressing IL-17C (IL-17C+) mice develop a psoriasiform skin phenotype. To investigate IL-17C-mediated inflammation, IL-17C+ mice were mated with IL-17RE-deficient (KO) mice and skin examined. IL-17C+IL-17REKO mice had similar acanthosis and T cell numbers as IL-17C+ mice (n=8/grp; P & gt;0.1), as did IL-17C+ mice transplanted with bone marrow from CD4-IL-17RE vs. WT mice (n=6–9; P & gt;0.1). These results suggest that IL-17C signaling is IL-17RE independent. Next, IL-17C+IL-17REKO mice were treated with anti-IL-17RA antibodies and a 54% reduction in acanthosis was observed (n=3; P=0.006), suggesting that IL-17C-IL-17RA signaling is critical for skin inflammation. In KC-Tie2 psoriasis mice, skin IL-17A and IL-17C increase ~15-fold (P & lt;0.05) and anti-IL-17A and anti-IL-17RA antibody treatment improves acanthosis and decreases CD4+ T cells (P & lt;0.05 vs. IgG, n=5–11/grp), with anti-IL-17RA having greater efficacy than anti-IL-17A (P=0.02). This suggests that both IL-17C and IL-17A signaling through IL-17RA are critical. Indeed, genetic deletion of IL-17C from KC-Tie2 mice led to a 67% and 58% decrease in acanthosis and CD4+ T cells, respectively (n=8/grp; P & lt;0.001 vs. KC-Tie2 mice). Finally, IL-17A modulation in IL-17C+ mice using anti-IL-17A antibodies, transplanting IL-17AKO bone marrow or introducing intradermal IL-17A, each had no effect on IL-17C+ skin inflammation. Our results demonstrate that IL-17C-mediated skin inflammation occurs in an IL-17RE independent, IL-17RA dependent manner and that a tiered balance between IL-17C-IL-17A-IL-17RA signaling may dictate levels of inflammation.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.198.Supp.61.2
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2017
detail.hit.zdb_id:
1475085-5
