Figure - PMC

Skip to main content

An official website of the United States government

Here's how you know

Here's how you know

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

View full-text article in PMC

. 2022 Dec 12;13:1056838. doi: 10.3389/fimmu.2022.1056838

Search in PMC
Search in PubMed
View in NLM Catalog
Add to search

Copyright © 2022 Poto, Gambardella, Marone, Schroeder, Mattei, Schiavoni and Varricchi

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

PMC Copyright notice

Schematic representation of the versatile role of basophils in the pathobiology of allergic disorders. Several immunological (i.e., allergens, superallergens, viral, bacterial and fungal proteins, cytokines) and non-immunological stimuli (e.g., pollutants, diesel exhaust particles) activate mucosal (i.e., lung and gut) and skin barriers to release different alarmins (i.e., TSLP, IL-33, IL-25) (130, 216, 217). Alarmins activate group 2 innate lymphoid cells (ILC2s) through the engagement of specific receptors (TSLPR, ST2, IL-25R, respectively) (218, 219) to release IL-5 and CCL11 that promote eosinophil infiltration into inflamed tissue (220, 221). Human and mouse basophils express the high-affinity receptor for IgE (FcεRI) (36, 37) and the receptors for IL-3 (IL-3Rα/CD123) (34, 44), GM-CSF (CD116) (45, 46), IL-33 (ST2/IL1RL1) (47–50), IL-5 (CD125) (51) and a variety of chemokine receptors (5, 55–60). The TSLP receptor (TSLPR/IL-7Rα) is expressed by mouse basophils (12, 34), but its presence on basophils from allergic and healthy donors remains controversial (12, 14–16). TSLP activates mouse but not human basophils (12, 17). IL-3 plays a key role in the development, survival and activation of human and mouse basophils (17). IL-3 activates human and mouse basophils to release cytokines and chemokines (12, 17, 46, 222). IgE-FcεRI crosslinking by antigens, superallergens and functional anti-IgE autoantibodies activates basophils to release a wide spectrum of inflammatory and immunomodulatory factors (24, 70, 75, 76, 78, 79, 134, 211, 223). IL-33 activates human and mouse basophils to release several cytokines and chemokines (12). Activated human (12, 24, 74–82) and mouse (12, 47, 80) basophils secrete large amounts of IL-4. Both human (12, 75, 76, 78, 81–85) and mouse basophils (12, 47) also release IL-13. Human basophils secrete several angiogenic factors such as vascular endothelial growth factor-A (VEGF-A) (64). Basophil-derived IL-4 activates ILC2s to enhance the release of IL-5 and CCL11, leading to eosinophil infiltration (68). IL-4 promotes Th2 cell differentiation and enhances humoral immune responses (224). IL-4, together with IL-13, induces T follicular helper cells (Tfh) to promote IgE responses (225, 226). Basophil-derived IL-4 and IL-13 act on inflammatory monocytes inducing their differentiation into M2 macrophages (227). IL-4 and IL-13 activate fibroblasts to promote the production of chemokines (CCL5 and CCL11) (228) and collagen (229). IL-4 and IL-13 and vasoactive mediators (histamine, LTC₄, VEGF-A) act on blood endothelial cells (64, 230) to upregulate the expression of vascular cell adhesion molecule-1 (VCAM-1) (231), leading to enhanced trans-endothelial migration of eosinophils and basophils (186).