TY  - JOUR
AU  - Chaly, Y
AU  - Barr, JY
AU  - Sullivan, DA
AU  - Thomas, HE
AU  - Brodnicki, TC
AU  - Lieberman, SM
Y2  - 2020/12/09
Y1  - 2018/10/01
SN  - 1422-0067
UR  - http://hdl.handle.net/11343/253168
AB  - Nonobese diabetic (NOD) mice spontaneously develop lacrimal and salivary gland autoimmunity similar to human Sjögren syndrome. In both humans and NOD mice, the early immune response that drives T-cell infiltration into lacrimal and salivary glands is poorly understood. In NOD mice, lacrimal gland autoimmunity spontaneously occurs only in males with testosterone playing a role in promoting lacrimal gland inflammation, while female lacrimal glands are protected by regulatory T cells (Tregs). The mechanisms of this male-specific lacrimal gland autoimmunity are not known. Here, we studied the effects of Treg depletion in hormone-manipulated NOD mice and lacrimal gland gene expression to determine early signals required for lacrimal gland inflammation. While Treg-depletion was not sufficient to drive dacryoadenitis in castrated male NOD mice, chemokines (Cxcl9, Ccl19) and other potentially disease-relevant genes (Epsti1, Ubd) were upregulated in male lacrimal glands. Expression of Cxcl9 and Ccl19, in particular, remained significantly upregulated in the lacrimal glands of lymphocyte-deficient NOD-severe combined immunodeficiency (SCID) mice and their expression was modulated by type I interferon signaling. Notably, Ifnar1-deficient NOD mice did not develop dacryoadenitis. Together these data identify disease-relevant genes upregulated in the context of male-specific dacryoadenitis and demonstrate a requisite role for type I interferon signaling in lacrimal gland autoimmunity in NOD mice.
LA  - English
PB  - MDPI
T1  - Type I Interferon Signaling Is Required for Dacryoadenitis in the Nonobese Diabetic Mouse Model of Sjogren Syndrome
DO  - 10.3390/ijms19103259
IS  - International Journal of Molecular Sciences
VL  - 19
IS  - 10
L1  - /bitstream/handle/11343/253168/PMC6214106.pdf?sequence=1&isAllowed=y
ER  -