Cutting edge: the role of IFN-α receptor and MyD88 signaling in induction of IL-15 expression in vivo.
IL-15 plays a multifaceted role in immune homeostasis, but the unreliability of IL-15 detection has stymied exploration of IL-15 regulation in vivo. To visualize IL-15 expression, we created a transgenic mouse expressing emerald-GFP (EmGFP) under IL-15 promoter control. EmGFP/IL-15 was prevalent in innate cells including dendritic cells (DCs), macrophages, and monocytes. However, DC subsets expressed varying levels of EmGFP/IL-15 with CD8(+) DCs constitutively expressing EmGFP/IL-15 and CD8(-) DCs expressing low EmGFP/IL-15 levels. Virus infection resulted in IL-15 upregulation in both subsets. By crossing the transgenic mice to mice deficient in specific elements of innate signaling, we found a cell-intrinsic dependency of DCs and Ly6C(+) monocytes on IFN-α receptor expression for EmGFP/IL-15 upregulation after vesicular stomatitis virus infection. In contrast, myeloid cells did not require the expression of MyD88 to upregulate EmGFP/IL-15 expression. These findings provide evidence of previously unappreciated regulation of IL-15 expression in myeloid lineages during homeostasis and following infection.
Department of Immunology, Center for Integrated Immunology and Vaccine Research, University of Connecticut Health Center, Farmington, CT 06030, USA.
Sara L
SL
Colpitts
Thomas A
TA
Stoklasek
Courtney R
CR
Plumlee
Joshua J
JJ
Obar
Caiying
C
Guo
Leo
L
Lefrançois
D000818:Animals; D002469:Cell Separation; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D005434:Flow Cytometry; D019409:Interleukin-15 / Q000096:biosynthesis* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology / Q000378:metabolism; D053633:Receptor, Interferon alpha-beta / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D054243:Vesicular Stomatitis / Q000276:immunology
D019409:Interleukin-15; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D053633:Receptor, Interferon alpha-beta