The role of skin-derived IFN-kappa in the development of systemic autoimmunity
| Autor: | Jacob William Shelton Martens, Jianhua Liu, Mitra Maz, J Michelle Kahlenberg |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 208:108.01-108.01 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.208.supp.108.01 |
| Popis: | Aberrant type I interferon expression and downstream interferon-stimulated gene signatures are central to the immune dysregulation observed in lupus. Recent evidence has suggested that elevated interferon kappa expression in the skin originating from keratinocytes may precede the development of systemic autoimmunity. Using a transgene mouse model overexpressing IFN-κ specifically in keratinocytes, we observe the development of anti-nuclear antibodies and immune complex deposition in the kidneys in the absence of environmental triggers. We also observe immune cell infiltration in the kidneys including activated CD4 T cells, activated cDC2-like dendritic cells, and expansion of IgD-CD27-double negative B cells. A subset of DN B cells has recently been shown to be increased in the blood of lupus patients with active disease and nephritis. This DN B cell subset was shown to be hyperresponsive to TLR7 signaling and showed transcriptional markers indicative of an inclination to differentiate into antibody-secreting plasmablasts. Further studies on the IFN-κ induced DN B cells in our model are needed to confirm phenotype and function of these cells. Future studies also hope to address the role of individual immune cell types in propagating or responding to the skin IFN-κ signal. Elucidating the mechanisms of early immune dysregulation resulting from this heightened IFN signaling would provide promising clinical relevance to treating patients early in their disease course, potentially prior to detrimental systemic manifestations. Supported by NIAMS(R01 AR071384-05) NIH(T32 AI007413-29) |
| Databáze: | OpenAIRE |
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