Just How Important is IL-17 in Horses with RAO?

Investigations of equine recurrent airway obstruction have often been undertaken with the aim of characterizing the disease in the context of an aberrant CD4+ response (e.g. Th-1, Th-2). With the recognition of additional sub-populations of CD4+ cells (e.g.
Th-17, induced T-regulatory cells), it is logical to determine if these cell types are also involved in RAO. Th-17 cells are so named because they, along with CD8+ cells, γδT cells and granulocytes, produce the chemokine, interleukin-17 (IL-17, along with IL-17F, IL-21 and IL-22). IL-17 targets the airway epithelium6 and increases transcription of neutrophil chemoattractants such as CXCL1, CXCL8, CCL20, CSF-1, CSF-2 and ICAM-1. Depending upon the species, IL-17 transcription in CD4+ cells is regulated by IL-23, IL-6 and IL-1β. 9 Th-17 cells have been implicated in the pathogenicity of autoimmune disorders as well as in the development of inflammatory responses involving mucosal surfaces of the intestinal and respiratory tract. At such mucosal sites, increased expression of IL-17 and IL-23 are typically observed.7,8 In rodent studies, acute pulmonary neutrophilia is induced with instillation of IL-17 in the airways.5 Furthermore, in rodents the intranasal instillation of Aspergillus or Candida organisms enhances IL-23 gene and protein expression in dendritic cells; increases IL-17 gene and protein synthesis in lymphocytes and induces pulmonary neutrophilia.3,13 In horses, enhanced IL-17 gene expression in bronchoalveolar lavage (BAL) cells isolated from horses during the chronic phase of dusty hay exposure has been documented2,4,12 but the predominant cellular source of IL-17 gene expression (lymphocytes or granulocytes) was not determined in those studies […]