Interleukin-17A and Interleukin-17F: A Tale of Two Cytokines

Children's Hospital of Pittsburgh, Rangos Research Center, Pittsburgh, PA 15201, USA.
Immunity (Impact Factor: 19.75). 02/2009; 30(1):9-11. DOI: 10.1016/j.immuni.2008.12.010
Source: PubMed

ABSTRACT In this issue of Immunity, Ishigame et al. (2009) show that interleukin-17A (IL-17A) mediates autoimmunity whereas both IL-17A and IL-17F are required for mucosal immunity. IL-17A may be more pathologic by inducing proinflammatory cytokines.

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    • "The contrasting biological functions could be due to an approximate 10-fold more potent induction of cytokines by IL-17A as compared to IL-17F [35]. In support of this concept, a recent review by Dubin and Kolls [36] has suggested a model which emphasizes the bioactivities of these cytokines on myeloid versus nonmyeloid cells or macrophages versus CD4+ T cells discussed priorly. Therefore, it is the ability of IL-17A to induce stronger responses and affect a wider range of cellular targets, making it a more pathogenic cytokine. "
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    ABSTRACT: Interleukin-17A (IL-17A) and IL-17F have been shown to mediate a crucial crosstalk between the immune system and various epithelial tissues, stimulating various defensive mechanisms to bacterial infections. A number of studies have characterized the response to IL-17A and IL-17F of epithelial cells from airways, intestine, and skin, but not from the mammary gland. To evaluate the potential contribution of IL-17 to the immune defense of the mammary gland, we analyzed the effects of recombinant bovine IL-17A and IL-17F on primary bovine mammary epithelial cells (MEC) by quantitative PCR and ELISA. We found expression (mRNA) of the two components of the IL-17 receptor complex, IL-17RA and IL-17RC, in mammary tissue and MEC in vitro. The expression of a number of genes encoding cytokines, chemokines and proteins endowed with antibacterial activities was increased by IL-17A, and to a lesser extent by IL-17F, but the magnitude of responses was modest. As expected, responses were augmented by the combination of IL-17A or IL-17F with TNF-α. Interestingly, responses of a few of the tested genes, such as IL8, CCL20, iNOS, and CfB, were augmented by the combination of IL-17A with staphylococcal lipoteichoic acid or muramyl dipeptide, bacterial agonists of the innate immune system. This can be interpreted as indicating that IL-17A and IL-17F are tailored to exert their full potential in a septic environment. MEC responses were characterized by the expression of chemokines targeting not only neutrophils (CXCL3 and CXCL8) but also mononuclear leucocytes (CCL2, CCL20). Production of IL-6 was low and the inflammatory cytokines TNF-α and IL-1β were expressed (mRNA) but proteins were not secreted. Altogether, our results suggest that IL-17A and IL-17F have a potential to modulate the mammary gland immune response to mastitis-causing pathogens.
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