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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Colpitts, Sara L. Puddington, Lynn Lefrançois, Leo |
| Description | Author Affiliation: Colpitts SL ( Department of Immunology, Center for Integrated Immunology and Vaccine Research, UConn Health, Farmington, CT 06030 puddington@uchc.edu Sara.L.Colpitts@Dartmouth.edu.); Puddington L ( Department of Immunology, Center for Integrated Immunology and Vaccine Research, UConn Health, Farmington, CT 06030 puddington@uchc.edu Sara.L.Colpitts@Dartmouth.edu.); Lefrançois L ( Department of Immunology, Center for Integrated Immunology and Vaccine Research, UConn Health, Farmington, CT 06030.); |
| 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-15R , in the development of IL-17-producing γδ (γδ-17) T cells. Phenotypic analysis has shown that CD44(high) γδ-17 cells express IL-15R and the common gamma chain (CD132), yet lack the IL-2/15Rß chain (CD122). Surprisingly, we found an enlarged population of γδ-17 cells in the peripheral and mesenteric lymph nodes of adult IL-15R KO mice, but not of IL-15 KO mice. The generation of mixed chimeras from neonatal thymocytes indicated that cell-intrinsic IL-15R 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-15R intracellular signaling domain was replaced with the intracellular portion of the IL-2R 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-15R , were increased in newborn mice deficient in IL-15R signaling, but not in IL-15 itself. Thus, these findings demonstrate that signaling through IL-15R regulates the development of γδ-17 cells early in ontogeny, with long-term effects on their peripheral homeostasis in the adult. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 31 |
| Volume Number | 112 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2015-08-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Interleukin-15 Receptor Alpha Subunit Metabolism Interleukin-17 Biosynthesis Receptors, Antigen, T-Cell, Gamma-delta Signal Transduction T-Lymphocytes Cytology Animals Animals, Newborn Antigens, CD Cell Movement Fluorescence Deficiency Interleukin-2 Receptor Alpha Subunit Mice, Inbred C57BL Mice, Knockout Thymus Gland Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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