Senescence-associated tertiary lymphoid structures in Sjögren's disease model nishiura mice

ABSTRACT We discovered a Sjögren's disease (SjD)-like state in the programmed cell death 1 + (PD-1⁺) niches of the spleen and submandibular glands of 36-week-old female Nishiura (NI) mice, characterized by the formation of tertiary lymphoid structures (TLS) by senescence-associated (SA) immune cells, production of anti-α-amylase autoantibodies, and reduced saliva secretion. Co-culturing B220⁺/PD-1⁺ cells derived from the spleens of NI mice with CD4 + /PD-1 + /CD153 + (SA-Tfh) cells for 48 hours enhanced IgG and senescence-associated secretion phenotype production in both cell types. Conversely, transplantation of spleen-derived SA-Tfh cells from NI mice expanded TLS in the submandibular glands of recipient mice. Meanwhile, a retrospective histopathological cohort study of seven SjD patients aged 50–70 revealed that the fibrogenic capacity per SA-Tfh cell significantly increased with age. Collectively, these data suggest that TLS formation associated with SA immune cells in the submandibular glands is a key mechanism in SjD.