Translating the biology of B common receptor- engaging cytokines into clinical medicine

The family of cytokines that comprises IL-3, IL-5, and GM-CSF was discovered over 30 years ago, and their biological activities and resulting impact in clinical medicine has continued to expand ever since. Originally identified as bone marrow growth factors capable of acting on hemopoietic progenitor cells to induce their proliferation and differentiation into mature blood cells, these cytokines are also recognized as key mediators of inflammation and the pathobiology of diverse immunologic diseases. This increased understanding of the functional repertoire of IL-3, IL-5, and GM-CSF has led to an explosion of interest in modulating their functions for clinical management. Key to the successful clinical translation of this knowledge is the recognition that these cytokines act by engaging distinct dimeric receptors and that they share a common signaling subunit called B-common or Bc. The structural determination of how IL-3, IL-5, and GM-CSF interact with their receptors and linking this to their differential biological functions on effector cells has unveiled new paradigms of cell signaling. This knowledge has paved the way for novel mAbs and other molecules as selective or pan inhibitors for use in different clinical settings. (J Allergy Clin Immunol 2023;151:324-44.)

Automated summary

The family of cytokines IL-3, IL-5, and GM-CSF, which was discovered over 30 years ago, continues to expand in its biological activities and impact on clinical medicine. These cytokines have been identified as bone marrow growth factors and are also recognized as key mediators of inflammation and immunologic diseases. The understanding of their functions has led to increased interest in modulating them for clinical management.