IL-17RC Is Required for Immune Signaling via an Extended SEF/IL-17R Signaling Domain in the Cytoplasmic Tail

Abstract

Material Supplementary 9.DC1http://www.jimmunol.org/content/suppl/2010/06/16/jimmunol.090373

Interleukin-17-Induced Protein Lipocalin 2 Is Dispensable for Immunity to Oral Candidiasis

“…Mice lacking either IL-17 receptor subunit (IL-17RA and IL-17RC) are highly susceptible to OPC. Similarly, mice lacking IL-23 (either the IL-12p40 or the IL-23p19 subunit), a cytokine that induces IL-17-producing cells, are also susceptible (7)(8)(9). In agreement with the findings for mice, humans with mutations in IL-17RA or its ligand IL-17F suffer from chronic mucocutaneous candidiasis (CMC), characterized by both OPC and dermal candidiasis (10).…”

“…Accordingly, WT or lcn2 Ϫ/Ϫ mice (27) were subjected to OPC for 5 days, and fungal loads in the oral mucosa were assessed as described above. As controls, we also used IL-23 Ϫ/Ϫ mice (which show the same susceptibility to OPC as IL-17RA Ϫ/Ϫ mice [8]). As an additional control, lcn2 Ϫ/Ϫ mice were immunosuppressed with high-dose cortisone acetate.…”

TRAF6-Dependent Act1 Phosphorylation by the IκB Kinase-Related Kinases Suppresses Interleukin-17-Induced NF-κB Activation

“…Act1 has been shown to be phosphorylated upon IL-17 stimulation (1,14,31). Act1 has also been shown to interact with IKK complex (20,21).…”

The Adaptor CARD9 Is Required for Adaptive but Not Innate Immunity to Oral Mucosal Candida albicans Infections

“…Immunity to oral candidiasis is strongly dependent on signals from IL-17, since mice and humans with defects in IL-17RA, IL-17RC, and Act1 (the major adaptor for the IL-17 pathway [29]) are exquisitely susceptible to CMC (6,20,21,30). Similarly, humans with neutralizing antibodies (Abs) against Th17 cytokines arising from autoimmune polyendocrinopathy syndrome-1 (AIRE deficiency) or certain thymomas are also prone to mucosal candidiasis (31)(32)(33).…”

“…Mice, in contrast, are naive to C. albicans and do not exhibit cross-reactive adaptive responses to other Candida species or yeast derivatives in food (17)(18)(19). However, mice mount rapid and powerful IL-17R-dependent responses to oral C. albicans infections, indicative of a strong innate response (20,21). Similarly to humans, mice exposed to C. albicans generate long-term adaptive Th17 cell responses that confer additional protection from infection (18,19).…”