Figure 1
A schematic representation of eosinophilia in the airways. The figure portrays (A) the complex eosinophil biology: Maturation: CD34+ myeloid progenitor cells (bone-marrow) differentiate into the IL5α+ CCR3+ eosinophil-committed progenitor cells under the influence of the different transcription factors like GATA2 and C/EBPα. IL-5, IL-3 and GM-CSF stimulate their further maturation into eosinophils. Migration: release into the circulation is coordinated synergistically by IL-5 and eotaxin. Transmigration: under the influence of IL-5 and eotaxin, the eosinophils ‘seep’ out through the endothelium. Recruitment: Eosinophil trafficking into the site of inflammation is selectively regulated by IL-5, eotaxin and CCL5, in addition to a multitude of cytokines. Activation: IL-5 binds to IL-5Rα and activates eosinophils to release a multitude of cytokines, eosinophilic granular proteins, cysteinyl leukotrienes, that lead to tissue damage and further aggravates the inflammatory process. Survival and stabilisation: IL-5 released from different sources and products from mast cell (MC) degranulation suppresses apoptosis and allows survival of eosinophils in the submucosa. (B) Different sources of IL-5 (in red) and sustenance of eosinophilia: (i) the canonical TH2 pathway initiated by dendritic cell (DC) activation releases IL-5. (ii) MC activation is another source of IL-5 that can be triggered by IgE binding to the FCϵRI receptor or by epithelial-derived Type 2 alarmins like TSLP and IL33; or via TH9 pathway (iii) Type-2 alarmins (IL-33, IL-25, TSLP) can activate the lineage negative ID2+ lymphoid cells resident in the tissue to differentiate into lineage negative ILC2s that can release IL-5 and IL-13, and drive eosinophilic inflammation (iv) IL-13 and IL-4 can recruit CD34+ progenitors cells from bone marrow into the lung tissue where it can differentiate into eosinophils in presence of IL-5. N.B. Diagram is not up to scale. Mechanisms relevant to only eosinophilic inflammation has been included.