IL-17A controls IL-17F production and maintains blood neutrophil counts in mice.
G-CSF, its receptor, and IL-17 receptor A (IL-17RA) are all required to maintain baseline neutrophil counts in mice. In this study, we tested whether IL-17F could compensate and maintain baseline neutrophil counts in the absence of IL-17A. Unlike the reduced neutrophil counts found in IL-17RA-deficient mice, neutrophil counts were mildly increased in IL-17A-deficient (Il17a(-/-)) animals. There was no evidence for infection or altered neutrophil function. Plasma G-CSF and IL-17F levels were elevated in Il17a(-/-) compared with wild-type mice. IL-17F was mainly produced in the spleen and mesenteric lymph nodes, but IL-23 was unaltered in Il17a(-/-) mice. Instead, Il17a(-/-) splenocytes differentiated with IL-6, TGF-beta, and IL-23 ex vivo produced significantly more IL-17F in response to IL-23 than wild-type cells. Adding rIL-17A to Il17a(-/-) splenocyte cultures reduced IL-17F mRNA and protein secretion. These effects were also observed in wild-type but not IL-17RA-deficient cells. We conclude that IL-17A mediated suppression of IL-17F production and secretion requires IL-17RA and is relevant to maintain the normal set point of blood neutrophil counts in vivo.
von Vietinghoff
Sibylle
S
Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA. Sibylle@liai.org
Ley
Klaus
K
D000818:Animals; D001773:Blood Cells; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood; D006487:Hemostasis; D020381:Interleukin-17 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000097:blood / Q000172:deficiency / Q000502:physiology*; D007958:Leukocyte Count; D008198:Lymph Nodes / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000166:cytology*; D053722:Receptors, Interleukin-17 / Q000502:physiology; D013154:Spleen / Q000378:metabolism
D020381:Interleukin-17; D053722:Receptors, Interleukin-17; D016179:Granulocyte Colony-Stimulating Factor