title: IL-15 receptor α signaling constrains the development of IL-17-producing γδ T cells.
abstract: The development and homeostasis of γδ T cells is highly dependent on distinct cytokine networks. Here we examine the role of IL-15 and its unique receptor, IL-15Rα, in the development of IL-17-producing γδ (γδ-17) T cells. Phenotypic analysis has shown that CD44(high) γδ-17 cells express IL-15Rα and the common gamma chain (CD132), yet lack the IL-2/15Rβ chain (CD122). Surprisingly, we found an enlarged population of γδ-17 cells in the peripheral and mesenteric lymph nodes of adult IL-15Rα KO mice, but not of IL-15 KO mice. The generation of mixed chimeras from neonatal thymocytes indicated that cell-intrinsic IL-15Rα expression was required to limit IL-17 production by γδ T cells. γδ-17 cells also were increased in the peripheral lymph nodes of transgenic knock-in mice, where the IL-15Rα intracellular signaling domain was replaced with the intracellular portion of the IL-2Rα chain (that lacks signaling capacity). Finally, an analysis of neonatal thymi revealed that the CD44(lo/int) precursors of γδ-17 cells, which also expressed IL-15Rα, were increased in newborn mice deficient in IL-15Rα signaling, but not in IL-15 itself. Thus, these findings demonstrate that signaling through IL-15Rα regulates the development of γδ-17 cells early in ontogeny, with long-term effects on their peripheral homeostasis in the adult.
authors.affiliation: Department of Immunology, Center for Integrated Immunology and Vaccine Research, UConn Health, Farmington, CT 06030 puddington@uchc.edu Sara.L.Colpitts@Dartmouth.edu.
authors.forename: Sara L
authors.initials: SL
authors.lastname: Colpitts
authors.affiliation: Department of Immunology, Center for Integrated Immunology and Vaccine Research, UConn Health, Farmington, CT 06030 puddington@uchc.edu Sara.L.Colpitts@Dartmouth.edu.
authors.forename: Lynn
authors.initials: L
authors.lastname: Puddington
authors.affiliation: Department of Immunology, Center for Integrated Immunology and Vaccine Research, UConn Health, Farmington, CT 06030.
authors.forename: Leo
authors.initials: L
authors.lastname: Lefrançois
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015703:Antigens, CD / Q000378:metabolism; D002465:Cell Movement; D005453:Fluorescence; D053720:Interleukin-15 Receptor alpha Subunit / Q000172:deficiency / Q000378:metabolism*; D020381:Interleukin-17 / Q000096:biosynthesis*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology
chemical_list: D015703:Antigens, CD; D053720:Interleukin-15 Receptor alpha Subunit; D020381:Interleukin-17; D053645:Interleukin-2 Receptor alpha Subunit; D016692:Receptors, Antigen, T-Cell, gamma-delta
keywords: IL-15Rα; IL-17; γδ T cells