{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CCL26 (also known as eotaxin‐3) is a Th2‐associated chemokine that has emerged as a key effector in allergic inflammation. In eosinophilic esophagitis (EoE), for example, CCL26 is one of the most highly induced genes in esophageal tissue and its expression is strongly driven by IL‑13 through a STAT6‐dependent transcriptional mechanism. This induction correlates with tissue eosinophilia and mast cell infiltration, thereby implicating CCL26 as a critical mediator of the eosinophilic inflammatory response in EoE."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its well‐established role as a chemoattractant acting via CCR3 on eosinophils, CCL26 exhibits a broader range of immunomodulatory functions. Notably, it can bind to other chemokine receptors such as CCR2, where it functions as a natural antagonist by inhibiting MCP‑1–mediated monocyte responses and even promoting reverse migration. This antagonistic behavior is further extended to CCR1 and CCR5, while CCL26 also acts as an agonist on CX3CR1‐expressing cytotoxic lymphocytes and monocytes, suggesting a modulatory role in recruiting and reshaping broader immune cell trafficking."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, under hypoxic conditions in the tumor microenvironment, cancer cells upregulate CCL26 expression, which promotes the recruitment of myeloid‐derived suppressor cells (MDSCs) and contributes to immunosuppression and tumor progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies underscore that CCL26 is a multifunctional chemokine that not only drives eosinophil recruitment in allergic diseases such as EoE, but also modulates the trafficking and function of other immune cells via diverse receptor interactions. This versatility makes CCL26 an attractive target for therapeutic intervention in inflammatory and neoplastic disorders.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Carine Blanchard, Ning Wang, Keith F Stringer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Eotaxin-3 and a uniquely conserved gene-expression profile in eosinophilic esophagitis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI26679"}], "href": "https://doi.org/10.1172/JCI26679"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16453027"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16453027"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Carine Blanchard, Melissa K Mingler, Maria Vicario, et al. 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