OP0042 BLOCKING OF CD103+ TISSUE RESIDENT MEMORY T CELLS (TRM) AS A THERAPEUTIC STRATEGY IN SJOGREN’S SYNDROME

Background: Tissue-resident memory T cells (TRM), are a recently identified population featuring tissue localization and expression of markers homing, CD69 CD103. Recently, the expansion CD8+ TRMs their involvement in sialadenitis was described murine model SS. However, CD4+ TRM’s functional relevance pSS is still not fully understood, TRM therapeutic targeting unexplored. Objectives: The study aimed to address role CD4 + CD8 pathogenesis explore residency marker Methods: An animal experimental (ESS) obtained by immunization female C57BL/6 mice (n=10) with salivary glands (SG) protein extract Freund’s complete adjuvant used investigate dynamic infiltration SG TRMs, frequency, impact CD103 blockade. For intervention, at 10-weeks post-immunization, gland cannulated via Wharton’s duct, an anti-CD103 neutralizing antibody or vehicle-injected. mice’s saliva flow rate assessed, SGs were analyzed Flow-cytometry immunohistochemistry (IHC). frequency minor sicca syndrome (nSS) patients (n=39) cytometry IHC. genes involved retention assessed RT-PCR. Results: Upon ESS progression, significant progressive increase CD45 CD103+ observed from 5wk 20wk post-immunization (p<0.001), where most abundant, followed . Consistently, detected within lymphocytic mice. Sorted purified CD10 CD3 showed higher Granzyme B, TNF-alpha compared - both mRNA levels. Notably, treated improvement function (p<0.05) reduced infiltrations measured as focus score (FS) (p<0.01) area-fraction (p<0.01). treatment consistently IFN-gamma , B +, TNFa cells. We next performed phenotypic analysis immune observing (p<0.05). Finally, IHC that accompanied down-regulation E-cadherin glandular migration outside epithelium context inflammatory infiltrates. up-regulation BLIMP1, KFL-2, S1PR1 ITGB2. CXCL9 CXCL10, IL-15 recruitment long-term survival significantly modulated glands. Conclusion: expanded activated ESS, participating organization inflammation. Although mechanisms behind this could be valuable novel target prevent destruction Sjogren syndrome. Disclosure Interests: None declared