Imaging Changes and Immune-Checkpoint Expression on T Cells in Bronchoalveolar Lavage Fluid from Patients with Pulmonary Sarcoidosis.

Yasuaki Kotetsu,Kentaro Hata,Masako Arimura-Omori,Kunihiro Suzuki,Daisuke Eto,Hiroyuki Ando,Toyoshi Yanagihara,Yuzo Yamamoto,Eiji Harada,Naoki Hamada

doi:10.3390/biomedicines9091231

Yasuaki Kotetsu, Kentaro Hata + Show 8 more

Open Access

https://doi.org/10.3390/biomedicines9091231

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Journal: Biomedicines	Publication Date: Sep 16, 2021
Citations: 1	License type: CC BY 4.0

Affiliation: Kyushu University, Hamanomachi Hospital

Abstract

Sarcoidosis is a systemic, granulomatous disease caused by unknown immunological abnormalities. The organs most vulnerable to sarcoidosis are the lungs. Patients often resolve spontaneously, but the lungs can also be severely affected. Although details regarding prognostic factors in sarcoidosis patients with lung involvement remain unclear, several reports have suggested that immune checkpoint molecules are involved in the pathogenesis of sarcoidosis. In this study, we divided sarcoidosis patients into two groups based on chest computed tomography (CT) findings and compared immune checkpoint molecules expressed on T cells in bronchoalveolar lavage fluid (BALF) in the two groups, using flow cytometry. We found elevated programmed cell death 1 (PD-1) or T cell immunoglobulin- and mucin-domain-containing molecule-3 (TIM-3) expression on T cells in BALF in patients with spontaneous improvement in CT findings, compared with those in patients without improvement in CT findings. In conclusion, our study implies that PD-1 or TIM-3 expression on T cells in BALF may be a prognostic factor for pulmonary lesions in sarcoidosis.

Highlights

Sarcoidosis is a granulomatous disease that can develop in almost any organ, but the organs most vulnerable to sarcoidosis are the lungs [1]
Sarcoidosis has been known for a long time, but a detailed understanding of factors leading to spontaneous resolution of the imaging findings of this disease does not yet exist
It has been reported that the expression of programmed cell death 1 (PD-1) on CD4+ T cells in bronchoalveolar lavage fluid (BALF) is higher in patients with sarcoidosis than in healthy controls [12], but it has been uncertain whether differences in PD-1 expression level are associated with changes in imaging findings

Summary

Introduction

Sarcoidosis is a granulomatous disease that can develop in almost any organ, but the organs most vulnerable to sarcoidosis are the lungs [1]. Sarcoidosis has been known for a long time, but a detailed understanding of factors leading to spontaneous resolution of the imaging findings of this disease does not yet exist. It has been reported that restoration of CD4+ subset function is associated with spontaneous clinical resolution of pulmonary sarcoidosis [3]. When T cell receptor binding to antigen/major histocompatibility complex (MHC) is accompanied by the involvement of immune checkpoint molecules, T cell activation is suppressed [4]. We hypothesize that these immune checkpoint molecules may participate in the pathogenesis of sarcoidosis and that expression of these molecules on Tcells in the affected organ (lung) may influence the prognosis of sarcoidosis. We focus on the following proteins: programmed cell death 1 (PD-1), a negative regulator of activated

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