Monocytes in Lupus Pathogenesis

Baylor Research Institute, Dallas TX

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Abstract

Healthy blood monocytes are immunologically quiescent cells. We found that monocytes isolated[unreadable] from the blood of SLE patients have dendritic cell (DC) function that could partially be ascribed to Type IIFN.[unreadable] Comparison of transcriptional patterns of healthy and SLE monocytes revealed the differential expression of[unreadable] 982 transcripts of which 1) 608 were due to Type I IFN exposure, 2) 116 could not be ascribed to Type I IFN[unreadable] but were also expressed in healthy blood myeloid DCs (mDCs), and 3) 258 were neither type I IFN nor[unreadable] mDCs genes which we call unique SLE monocytes transcription patterns. Thus, SLE monocytes carry type I[unreadable] IFN-related and unrelated transcriptional signatures which might reflect alterations in other blood cell[unreadable] compartments and provide explanation for altered B cell compartment. Therefore, we propose a hypothesis[unreadable] that SLE monocytes are central to etiopathogenesis of SLE. We have designed three aims to test our[unreadable] hypothesis: Aim 1 will identify markers of SLE monocytes that can be used in patients follow-up. Aim[unreadable] 2 will determine factors that trigger SLE monocytes transcription patterns. We will establish if cells[unreadable] (neutrophils or plasmacytoid DCs) and/or cell products (immune complexes) contribute to SLE monocytes[unreadable] phenotype and function. We will also assess therapeutic effect of ImmunoRegulatory ODN. Aim 3 will[unreadable] demonstrate that SLE monocytes activate B cells. Thus, the research plan that we propose here will[unreadable] generate: 1) markers for disease follow up and response to therapy; and 2) novel molecules relevant for[unreadable] disease pathogenesis and novel therapeutic targets.