Eosinophils and IL-9 promote mast cell accumulation in pediatric eosinophilic esophagitis
Published Online: May 1, 2013
Eosinophilic esophagitis (EoE) is a chronic allergic disease that is defined by a diffuse and robust infiltration of the esophagus by eosinophils. Eosinophils depend on interleukin-5 (IL-5) for their generation in the bone marrow, their accumulation in target tissues, and their subsequent activation. Once in the esophagus, eosinophils make growth factors and cytokines that can promote the survival of other inflammatory cells. In addition to eosinophils, other types of inflammatory cells such as mast cells are found in large numbers in the EoE esophagus. Like eosinophils, mast cells produce growth factors such as transforming growth factor beta-1 (TGFb1) which can cause both fibrosis and smooth muscle cell contraction. However, the factors that regulate mast cell accumulation in the EoE esophagus are not clear.
In an original article in The Journal of Allergy and Clinical Immunology (JACI), Otani et al demonstrate that eosinophilic and non-eosinophilic inflammatory cells make the mast cell attractant and growth factor IL-9. The investigators discovered this by using biopsies from a multicenter study that treated pediatric EoE subjects with anti-IL-5. Treatment with anti-IL-5 specifically decreases eosinophils. The reduction in eosinophils correlated with decreases in mast cell numbers, suggesting that eosinophils may be partially responsible for mast cell accumulation and survival in the esophagus. Supportive of this hypothesis, mast cells and eosinophils lived in clusters where a single mast cell was surrounded by multiple eosinophils in close proximity. Following treatment with mepolizumab, an anti-IL-5 antibody, these clusters were significantly decreased. By using fluorescent stains, the authors demonstrated that eosinophils were a large population of the cells that made IL-9.
This study has a number of potentially important clinical implications. It demonstrates the eosinophil is an integral piece of the inflammatory puzzle in EoE and that by specifically removing the eosinophil using an anti-IL-5 antibody, there are secondary effects on other cells such as mast cells. In addition, this study shows, for the first time, that IL-9 is present and likely to be important in the pathogenesis of EoE. As such, IL-9 may provide a new therapeutic target in EoE.
The Journal of Allergy and Clinical Immunology (JACI) is the official scientific journal of the AAAAI and is the most cited journal in the field of allergy and clinical immunology