Synergy between Hematopoietic and Radioresistant Stromal Cells Is Required for Autoimmune Manifestations of DNase II-/-IFNaR-/- Mice
Authors
Baum, RebeccaNundel, Kerstin
Pawaria, Sudesh
Sharma, Shrutie
Busto, Patricia
Fitzgerald, Katherine A.
Gravallese, Ellen M.
Marshak-Rothstein, Ann
UMass Chan Affiliations
Division of Infectious Diseases and Immunology, Department of MedicineProgram in Innate Immunity
Division of Rheumatology, Department of Medicine
Document Type
Journal ArticlePublication Date
2016-02-01
Metadata
Show full item recordAbstract
Detection of endogenous nucleic acids by cytosolic receptors, dependent on STING, and endosomal sensors, dependent on Unc93b1, can provoke inflammatory responses that contribute to a variety of autoimmune and autoinflammatory diseases. In DNase II-deficient mice, the excessive accrual of undegraded DNA leads to both a STING-dependent inflammatory arthritis and additional Unc93b1-dependent autoimmune manifestations, including splenomegaly, extramedullary hematopoiesis, and autoantibody production. In this study, we use bone marrow chimeras to show that clinical and histological inflammation in the joint depends upon DNase II deficiency in both donor hematopoietic cells and host radioresistant cells. Additional features of autoimmunity in these mice, known to depend on Unc93b1 and therefore endosomal TLRs, also require DNase II deficiency in both donor and host compartments, but only require functional TLRs in the hematopoietic cells. Collectively, our data demonstrate a major role of both stromal and hematopoietic cells in all aspects of DNA-driven autoimmunity. These findings further point to the importance of cytosolic nucleic acid sensors in creating an inflammatory environment that facilitates the development of Unc93b1-dependent autoimmunity.Source
J Immunol. 2016 Feb 1;196(3):1348-54. doi: 10.4049/jimmunol.1502130. Epub 2016 Jan 4. Link to article on publisher's site
DOI
10.4049/jimmunol.1502130Permanent Link to this Item
http://hdl.handle.net/20.500.14038/28944PubMed ID
26729810Related Resources
ae974a485f413a2113503eed53cd6c53
10.4049/jimmunol.1502130