The Role of Extracellular Nuclear Molecules in the Pathogenesis of Autoimmune Disease

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Background

Among components in the blood, nuclear molecules have important properties that can impact on the pathogenesis of many autoimmune and inflammatory diseases. These molecules include (i) DNA; (ii) RNA; (iii) proteins and (iv) complexes of proteins and nucleic acid. Extracellular nuclear molecules likely originate from dead and dying cells although activation can also lead to extracellular translocation events in some circumstances. Among processes that can lead to the translocation of extracellular nuclear molecules, NETosis, which occurs with myeloid cells following certain activation events, may have a special contribution to autoimmunity by forming neutrophil extracellular traps (NETs); NETs can damage endothelium as well as serve as a source of cellular antigen.

While studies on extracellular nuclear molecules tend to focus on the role of individual biochemical entities (e.g., DNA and histones), in vitro and in vivo studies indicate that these molecules can exist in the form of higher ordered structures known as extracellular vesicles (EVs). EVs emanate from cells during cell activation and cell death and can be categorized into various types on the basis of size, biochemical composition, and presumed role of extracellular generation. Importantly, EVs contain nuclear as well as cytoplasmic molecules in a membrane-bound form. Together, extracellular nuclear molecules and EVs can promote inflammation and thrombosis as well as the transmission of information for gene expression. Given their potential role in disease, extracellular nuclear molecules are emerging as important biomarkers.

At present, research on extracellular nuclear molecules is rapidly expanding and providing novel insights into the pathogenesis of autoimmunity. In this Research Topic, we aim to provide a unique opportunity to present, in one place, a series of articles devoted to the full range of extracellular nuclear molecules and structures that have activities relevant to autoimmunity. We aim to collect an ensemble of Reviews and Mini-Reviews to provide an overall perspective on the field, while Original Research articles will present cutting-edge research in more focused areas. Given the nature of the field, Methods and Protocols are also welcomed since the assay of these molecules and structures can be challenging. A collation of methodology would serve the field well. We will also present an overview to summarize the major issues in the field and highlight key advances discussed in the articles and reviews.

The articles in this Research Topic will cover several issues including the following:

(i) The generation of extracellular nuclear molecules;
(ii) The cellular processes leading to extracellular translocation of nuclear molecules;
(iii) The role of extracellular nuclear molecules in autoimmune disease;
(iv) The biochemical and physical chemical properties of extracellular nuclear molecules;
(v) The assay of extracellular nuclear molecules;
(vi) The structure and function of EVs containing nuclear molecules and their impact on autoimmunity;
(vii) EVs as targets of autoreactivity;
(viii) Extracellular nuclear molecules as biomarkers of autoimmune disease and
(ix) Extracellular nuclear molecules as new therapeutic targets for treating autoimmune disease.

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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