Synergy between Hematopoietic and Radioresistant Stromal Cells Is Required for Autoimmune Manifestations of DNase II-/-IFNaR-/- Mice.

Citation data:

Journal of immunology (Baltimore, Md. : 1950), ISSN: 1550-6606, Vol: 196, Issue: 3, Page: 1348-54

Publication Year:
2016
Usage 36
Abstract Views 36
Captures 8
Readers 8
Social Media 5
Tweets 5
Citations 3
Citation Indexes 3
Repository URL:
https://escholarship.umassmed.edu/faculty_pubs/1171; https://works.bepress.com/katherine_fitzgerald/201; https://works.bepress.com/ellen_gravallese/81
PMID:
26729810
DOI:
10.4049/jimmunol.1502130
PMCID:
PMC4724517
Author(s):
Baum, Rebecca; Nundel, Kerstin; Pawaria, Sudesh; Sharma, Shrutie; Busto, Patricia; Fitzgerald, Katherine A.; Gravallese, Ellen M.; Marshak-Rothstein, Ann
Publisher(s):
The American Association of Immunologists
Tags:
Immunology and Microbiology; Immunology and Infectious Disease; Rheumatology
Most Recent Tweet View All Tweets
article description
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.