Human blood basophils produce interleukin-13 in response to IgE-receptor-dependent and -independent activation.
Interleukin-13 (IL-13) is a recently discovered immunoregulatory cytokine. The cellular sources of IL-13 and the regulation of its expression are largely unknown. Here we show that human basophils produce IL-13 in response to IgE-receptor (IgER) crosslinking, IL-3, IL-3 plus C5a, but not C5a alone. Human basophils express IL-13 in a restricted manner since, apart from IL-4, no other cytokines encoded on the cytokine gene cluster (IL-3, IL-5, and granulocyte macrophage-colony-stimulating factor [GM-CSF]), are induced. Highest levels of IL-13 are formed after IgE-independent activation leading to a prolonged secretion of IL-13. The response to IgER-cross-linking is more transient preferentially inducing IL-4, IL-3 is a unique cytokine regulating IL-13 production by human basophils: Among a large number of cytokines tested, only IL-3 is capable of directly inducing IL-13 expression. Furthermore, although some IL-13 is produced in response to C5a in the presence of IL-5, GM-CSF, IGF-1 or IL-1 beta, IL-3 is by far the most effective. IL-13 production was blocked by actinomycin D and cycloheximide and conditions leading to IL-13 release also lead to the induction of IL-13 mRNA. This study supports an important immunoregulatory role of human blood basophils, owing to their capacity to simultaneously express IL-13 and IL-4 in a restricted manner.
Ochensberger
B
B
Institute of Immunology and Allergology, Inselspital, Bern, Switzerland.
Daepp
G C
GC
Rihs
S
S
Dahinden
C A
CA
D001491:Basophils / Q000187:drug effects / Q000378:metabolism*; D015936:Complement C5a / Q000494:pharmacology*; D016207:Cytokines / Q000494:pharmacology; D004357:Drug Synergism; D005786:Gene Expression Regulation; D006801:Humans; D007152:Immunologic Capping; D018793:Interleukin-13 / Q000096:biosynthesis* / Q000235:genetics; D007377:Interleukin-3 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D017455:Receptors, IgE / Q000276:immunology*
D016207:Cytokines; D018793:Interleukin-13; D007377:Interleukin-3; D012333:RNA, Messenger; D017455:Receptors, IgE; D015847:Interleukin-4; D015936:Complement C5a