Introduction: Sarcoidosis, a systemic granulomatous disorder with unknow origin, is characterized by a chronic inflammation due to exaggerated immune response consisting of activated CD4-lymphocytes, in which activation is also regulated by immune checkpoint (IC) molecules. The aim was analyse the role and expression of PD1 and TIGIT on peripheral CD4 from patients affected by sarcoidosis at stage 2, idiopathic pulmonary fibrosis (IPF) and compared with healthy controls.

Methods: Patients followed at referral center for rare lung diseases of Siena university were enrolled. Peripheral blood samples were stained with monoclonal antibodies PD-1 and TIGIT though flow cytometry.

Results: Twelve sarcoidosis, twenty IPF patients and fifteen healthy controls were enrolled. PD-1 and TIGIT expression on CD4-positive cells were lower in HC than patient groups. TIGIT+CD4+ cell percentages were higher in sarcoidosis than IPF, while PD1+CD4+ cells were lower in sarcoidosis than IPF.

Conclusion: Sarcoidosis disease is characterized by an ongoing inflammation, due to an exaggerate activation and expression of T-cells providing a switching immune phenotype of T-cells. This explain the lymphocytes recruitment in the lung injury increasing the cytokines production. Spontaneous resolution occurs in 40-70% of sarcoidosis with stage II. Exploiting the synergy between PD-1/TIGIT axis, the anti-TIGIT target therapy could be helpful to avoid the progression of sarcoidosis.