Expansion of an Atypical NK Cell Subset in Mouse Models of Systemic Lupus Erythematosus
| Autor: | Elisaveta Voynova, Jeff Skinner, Silvia Bolland |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Male
Adoptive cell transfer Cellular differentiation Immunology Mice Transgenic Lymphocyte Activation Real-Time Polymerase Chain Reaction Article Mice Interleukin 21 Microscopy Electron Transmission Animals Lupus Erythematosus Systemic Immunology and Allergy Cytotoxic T cell Cell Lineage Oligonucleotide Array Sequence Analysis Mice Knockout Transplantation Chimera MHC class II biology Innate lymphoid cell Cell Differentiation Cell cycle Adoptive Transfer Immunohistochemistry Molecular biology Lymphocyte Subsets Cell biology Killer Cells Natural Disease Models Animal biology.protein Interleukin 12 Female |
| Zdroj: | The Journal of Immunology. 194:1503-1513 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1402673 |
| Popis: | Chronic inflammatory conditions, such as in autoimmune disease, can disturb immune cell homeostasis and induce the expansion of normally rare cell populations. In our analysis of various murine models of lupus, we detect increased frequency of an uncommon subset identified as NK1.1+CD11c+CD122+MHC class II+. These cells share characteristics with the NK cell lineage and with cells previously described as IFN-producing killer dendritic cells: 1) they depend on IL-15 and express E4BP4; 2) they are cytotoxic and produce type I and type II IFN upon activation; and 3) they are efficient APCs both through MHC class II expression and in cross-presentation to CD8s. These atypical NK cells are responsive to TLR stimulation and thus are most abundant in mice with high copy number of the Tlr7 gene. They are highly proliferative as assessed by in vivo BrdU incorporation. In adoptive transfer experiments they persist in high numbers for months and maintain their surface marker profile, indicating that this population is developmentally stable. Gene expression analyses on both mRNA and microRNAs show a modified cell cycle program in which various miR-15/16 family members are upregulated, presumably as a consequence of the proliferative signal mediated by the increased level of growth factors, Ras and E2F activity. Alternatively, low expression of miR-150, miR-181, and miR-744 in these cells implies a reduction in their differentiation capacity. These results suggest that cells of the NK lineage that undergo TLR stimulation might turn on a proliferative program in detriment of their full differentiation into mature NK cells. |
| Databáze: | OpenAIRE |
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