Salivary-gland-protective regulatory T-cell dysfunction underlies female-specific sialadenitis in the non-obese diabetic mouse model of Sjögren syndrome

Immunology
Jennifer Y BarrScott M Lieberman

Abstract

Immune cell-mediated destruction of salivary glands is a hallmark feature of Sjögren syndrome. Similar to the female predominance in humans, female non-obese diabetic (NOD) mice develop spontaneous salivary gland autoimmunity. However, in both humans and mice it is unclear what factors contribute to the initial immune infiltration of the salivary glands. Here, we used an adoptive transfer model of Sjögren syndrome to determine if female mice harbor a sex-specific defect in salivary-gland-protective regulatory T (Treg) cells. Transfer of cervical lymph node (LN) cells from female NOD mice into sex-matched NOD-severe combined immunodeficient (SCID) recipients resulted in sialadenitis, regardless of the presence or absence of Treg cells. In contrast, transfer of cervical LN cells from male NOD mice into sex-matched NOD-SCID recipients only resulted in sialadenitis when Treg cells were depleted before transfer, suggesting that male NOD mice have functional salivary-gland-protective Treg cells. Notably, the host environment affected the ability of Treg cells to prevent sialadenitis with testosterone promoting salivary gland protection. Treg cells from male mice did not protect against sialadenitis in female recipients. Testosterone ...Continue Reading

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Citations

Oct 24, 2018·International Journal of Molecular Sciences·Yury ChalyScott M Lieberman
Apr 12, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Kaustubh ParasharOlga J Baker
Feb 19, 2020·Current Rheumatology Reports·Kiley BaxJulian L Ambrus
Dec 17, 2020·International Journal of Molecular Sciences·Ivy L DebreceniScott M Lieberman
May 1, 2021·International Journal of Molecular Sciences·Merri-Grace AllredScott M Lieberman

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