Figure 6.

Mitochondria as a possible link between inflammation and immune microenvironment in pSS. (A, B) Differential gene expression analysis of damage-associated molecular patterns (A) and apoptosis (B) was conducted using the ggpubr package via the Wilcox test from the validation cohort. (C) Schematic diagram describing possible mechanisms on how mitochondria act as a bridge between inflammation and immune microenvironment in pSS. The inflammatory environment in salivary glands of pSS initiated by a multitude of promising factors, including pathogen, which can indirectly or directly cause mitochondrial dysfunction. (❶ Once cell damages, some molecules, such as cytochrome c, carried by mitochondria will be released into inappropriate compartments and serve as DAMPs, recognized by immune cells, and trigger immune responses; ❷ impaired five mitochondrial respiratory-chain complexes had reduced ATP production level through OXPHOS, which often lead to aggravated cell damage; and ❸ damaged mitochondria had been associated with abnormal mitochondrial energy metabolism, and it might further compromise epithelia cell survival. Consequently, a vicious pathological circle is activated, consisting of DAMP release, massive immune cell infiltration, and mitochondrial damage.) DAMPs: damage-associated molecular patterns, OXPHOS: oxidative phosphorylation system. (D) TEM of labial salivary gland tissue from our own cohort shows cytoplasmic lipid droplets (red arrows) and progressive swollen mitochondria in salivary epithelial cells as disease progress (red frame). (E) Immunohistochemical staining for Bcl-2 of paraffin-embedded labial salivary gland specimens. Scale bar = 100 μm.