Rescue of autophagy and lysosome defects in salivary glands of MRL/lpr mice by a therapeutic phosphopeptide

Journal of Autoimmunity
Baihui LiSylviane Muller

Abstract

Sjögren's syndrome is a multifactorial systemic autoimmune disorder characterized by lymphocytic infiltrates in exocrine organs. Patients present with sicca symptoms, such as extensive dry eyes and dry mouth, and parotid enlargement. Other serious complications include profound fatigue, chronic pain, major organ involvement, neuropathies and lymphomas. Current treatments only focus on relieving symptoms and do not target the origin of the disease, which is largely unknown. The question we addressed here was whether some defects exist in autophagy processes in Sjögren's syndrome and if they can be corrected or minimized using an appropriate mechanism-driven treatment targeting this central survival pathway. Using a recognized murine model of secondary Sjögren's syndrome, we identified molecular alterations of autophagy occurring in the salivary glands of MRL/lpr mice, and discovered that opposite (up- or down-regulated) autophagy events can arise in distinct organs of the same mouse strain, here in lymphoid organs and salivary glands. We showed further that the therapeutic P140 peptide, known to directly act on chaperone-mediated autophagy, rescued MRL/lpr mice from cellular infiltration and autophagy defects occurring in saliva...Continue Reading

Citations

Sep 4, 2019·Nature Reviews. Drug Discovery·Srinivasa Reddy BonamSylviane Muller
Aug 29, 2019·Journal of Dental Research·X HongH Y Yang
Apr 8, 2020·Journal of Immunology Research·Bin WangGuixiu Shi
Jun 7, 2019·Clinical Reviews in Allergy & Immunology·Carlo Selmi
Jul 10, 2020·Cell Death & Disease·Masayuki NoguchiJohn A Chiorini
Feb 6, 2021·Journal of Clinical Medicine·Erika Huijser, Marjan A Versnel
Feb 26, 2021·Inhalation Toxicology·Rebekah L Kendall, Andrij Holian
Apr 7, 2019·Trends in Molecular Medicine·Sruthi Vijaya Retnakumar, Sylviane Muller
May 2, 2021·Journal of Autoimmunity·Maud WilhelmSylviane Muller

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