TY - JOUR
T1 - Type I and II interferon receptors differentially regulate type 1 diabetes susceptibility in Male versus female NOD mice
AU - Carrero, Javier A.
AU - Benshoff, Nicholas D.
AU - Nalley, Kimberly
AU - Unanue, Emil R.
N1 - Funding Information:
Acknowledgments. The authors thank Katherine E. Frederick (Washington University in St. Louis) for maintaining the mouse colony. Funding. This work was funded by grants provided by the National Institute of Diabetes and Digestive and Kidney Diseases (DK-058177) and National Institute of Allergy and Infectious Diseases (AI-14551). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The laboratory receives general support from the Kilo Diabetes & Vascular Research Foundation (Special Award). Duality of Interest. No potential conflicts of interest relevant to this article were reported. Author Contributions. J.A.C. and E.R.U. designed and performed experiments, collected and analyzed data, and wrote and edited the manuscript. N.D.B. and K.N. designed and performed experiments and collected and analyzed data. J.A.C. and E.R.U. are the guarantors of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
PY - 2018/9/1
Y1 - 2018/9/1
N2 - The role of interferons, either pathogenic or protective, during autoimmune diabetes remains controversial. Herein, we examine the progression of diabetes in NOD mice lacking the type I (IFNAR) or type II (IFNGR) interferon receptor and, for the first time, in mice deficient in both receptors (double knockout [DKO]). All mice were bred, maintained, and monitored in a single specific pathogen-free facility with high female and low male diabetes incidence. Our expectation was that removal of interferon signaling would reduce autoimmune destruction. However, examination of diabetes incidence in the IFNAR- and IFNGR-deficient NOD mice showed a reduction in females and an increase in males. In DKO mice, diabetes occurred only in female mice, at decreased incidence and with delayed kinetics. These results show that interferons act as both positive and negative modulators of type 1 diabetes disease risk dependent on sex.
AB - The role of interferons, either pathogenic or protective, during autoimmune diabetes remains controversial. Herein, we examine the progression of diabetes in NOD mice lacking the type I (IFNAR) or type II (IFNGR) interferon receptor and, for the first time, in mice deficient in both receptors (double knockout [DKO]). All mice were bred, maintained, and monitored in a single specific pathogen-free facility with high female and low male diabetes incidence. Our expectation was that removal of interferon signaling would reduce autoimmune destruction. However, examination of diabetes incidence in the IFNAR- and IFNGR-deficient NOD mice showed a reduction in females and an increase in males. In DKO mice, diabetes occurred only in female mice, at decreased incidence and with delayed kinetics. These results show that interferons act as both positive and negative modulators of type 1 diabetes disease risk dependent on sex.
UR - http://www.scopus.com/inward/record.url?scp=85052710355&partnerID=8YFLogxK
U2 - 10.2337/db18-0331
DO - 10.2337/db18-0331
M3 - Article
C2 - 30084830
AN - SCOPUS:85052710355
SN - 0012-1797
VL - 67
SP - 1830
EP - 1835
JO - Diabetes
JF - Diabetes
IS - 9
ER -