Differential Roles of Interleukin-17A and -17F in Host Defense against Mucoepithelial Bacterial Infection and Allergic Responses

Abstract

Interleukin-17A (IL-17A) is a cytokine produced by T helper 17 (Th17) cells and plays important roles in the development of inflammatory diseases. Although IL-17F is highly homologous to IL-17A and binds the same receptor, the functional roles of this molecule remain largely unknown. Here, we demonstrated with Il17a(-/-), Il17f(-/-), and Il17a(-/-)Il17f(-/-) mice that IL-17F played only marginal roles, if at all, in the development of delayed-type and contact hypersensitivities, autoimmune encephalomyelitis, collagen-induced arthritis, and arthritis in Il1rn(-/-) mice. In contrast, both IL-17F and IL-17A were involved in host defense against mucoepithelial infection by Staphylococcus aureus and Citrobacter rodentium. IL-17A was produced mainly in T cells, whereas IL-17F was produced in T cells, innate immune cells, and epithelial cells. Although only IL-17A efficiently induced cytokines in macrophages, both cytokines activated epithelial innate immune responses. These observations indicate that IL-17A and IL-17F have overlapping yet distinct roles in host immune and defense mechanisms.

Ecto-Nucleoside Triphosphate Diphosphohydrolase 7 Controls Th17 Cell Responses through Regulation of Luminal ATP in the Small Intestine

“…rodentium is an enteric bacterium that colonizes the intestine of mice postinfection. Clearance of C. rodentium is shown to be dependent on Th17-related cytokines, such as IL-17 and IL-22 (48,49). Data showing that mice lacking IL-23, a critical cytokine for Th17 cell development, are highly susceptible to C. rodentium infection also indicate that Th17-related cytokines are critical for the resistance to intestinal C. rodentium infection (50).…”

“…Consistent with these facts, Entpd7 2/2 mice showing an increased number of Th17 cells in the small intestine are highly resistant to intestinal infection with C. rodentium. IL-22 and IL-17, which induce production of antibacterial peptides (REGIIIg and b-defensins) from intestinal ECs (48,51), are produced from other cell populations, such as innate lymphoid cells and gdT cells (52,53). Therefore, Th17 cells, together with an innate type of IL-17-producing cells, contribute to intestinal pathogens.…”

Interleukin‐17‐producing γδ T (γδ17) cells in inflammatory diseases

“…Interleukin‐17 plays protective roles against bacterial and fungal infection by recruiting neutrophils, activating T cells and inducing antimicrobial peptides and inflammatory cytokines 1, 4, 578 or Mycobacterium bovis BCG infection 79.…”

“…It plays a crucial role in the host defence against bacterial and fungal infection by inducing pro‐inflammatory cytokines and chemokines, recruiting neutrophils, and activating T cells and B cells 1, 2. Mice deficient for IL‐17RA are highly susceptible to Klebsiella pneumoniae 3 and IL‐17‐deficient mice are susceptible to bacterial and fungal infection 4, 5. Interleukin‐17 is also implicated in various inflammatory/autoimmune disease models such as experimental autoimmune encephalomyelitis (EAE), arthritis in IL‐1 receptor antagonist‐deficient (Il1rn –/– ) mice and imiquimod‐induced psoriatic dermatitis in mice 6, 7, 8, 9, 10.…”

Meta-analysis of Associations between Interleukin-17 Gene Polymorphisms and Risk of Gastric Cancer

“…IL-17A and IL-17F are important members of the IL-17 cytokine family preferentially produced by helper T 17 (Th17) cells, which are responsible for the pathogenic activity of the lineage of CD4+ effector cells and multiple proinflammatory mediators (Rutitzky et al, 2005;Ishigame et al, 2009 et al, 2010). However, subsequent replication studies for the association between IL-17A and IL-17F variants and gastric cancer risk are controversial (Shibata et al, 2009;Arisawa et al, 2012;Rafiei et al, 2013;Zhang et al, 2014;Zhu et al, 2014).…”