Toll-Like Receptor 7 Is Required for Lacrimal Gland Autoimmunity and Type 1 Diabetes Development in Male Nonobese Diabetic Mice

被引:15
|
作者
Debreceni, Ivy L. [1 ,2 ]
Chimenti, Michael S. [3 ]
Serreze, David, V [4 ]
Geurts, Aron M. [5 ,6 ]
Chen, Yi-Guang [7 ,8 ]
Lieberman, Scott M. [1 ,2 ]
机构
[1] Univ Iowa, Carver Coll Med, Stead Family Dept Pediat, Iowa City, IA 52242 USA
[2] Univ Iowa, Immunol Grad Program, Iowa City, IA 52242 USA
[3] Univ Iowa, Carver Coll Med, Iowa Inst Human Genet, Iowa City, IA 52242 USA
[4] Jackson Lab, Bar Harbor, ME 04609 USA
[5] Med Coll Wisconsin, Dept Physiol, Milwaukee, WI 53226 USA
[6] Med Coll Wisconsin, Cardiovasc Ctr, Milwaukee, WI 53226 USA
[7] Med Coll Wisconsin, Dept Pediat, Dept Microbiol & Immunol, Milwaukee, WI 53226 USA
[8] Med Coll Wisconsin, Max McGee Natl Res Ctr Juvenile Diabet, Milwaukee, WI 53226 USA
基金
美国国家卫生研究院;
关键词
Sjö gren syndrome; type; 1; diabetes; Toll-like receptor 7; lacrimal gland; salivary gland; SJOGRENS-SYNDROME; T-CELLS; INTERFERON-GAMMA; GENE-EXPRESSION; INNATE IMMUNITY; MOUSE MODELS; DACRYOADENITIS; PATHOGENESIS; BIAS; TRANSCRIPTION;
D O I
10.3390/ijms21249478
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Sjogren syndrome (SS) is an immunologically complex, chronic autoimmune disease targeting lacrimal and salivary glands. Nonobese diabetic (NOD) mice spontaneously develop inflammation of lacrimal and salivary glands with histopathological features similar to SS in humans including focal lymphocytic infiltrates in the affected glands. The innate immune signals driving lymphocytic infiltration of these glands are not well-defined. Here we evaluate the role of Toll-like receptor (TLR) 7 in the development of SS-like manifestations in NOD mice. We created a Tlr7 knockout NOD mouse strain and performed histological and gene expression studies to characterize the effects of TLR7 on autoimmunity development. TLR7 was required for male-specific lacrimal gland inflammation but not for female-specific salivary gland inflammation. Moreover, TLR7 was required for type 1 diabetes development in male but not female NOD mice. RNA sequencing demonstrated that TLR7 was associated with a type I interferon (IFN) response and a type I IFN-independent B cell response in the lacrimal glands. Together these studies identify a previously unappreciated pathogenic role for TLR7 in lacrimal gland autoimmunity and T1D development in male NOD mice adding to the growing body of evidence supporting sex differences in mechanisms of autoimmune disease in NOD mice.
引用
收藏
页码:1 / 19
页数:19
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