AUTHOR=Hata Kentaro , Yanagihara Toyoshi , Matsubara Keisuke , Kunimura Kazufumi , Suzuki Kunihiro , Tsubouchi Kazuya , Eto Daisuke , Ando Hiroyuki , Uehara Maki , Ikegame Satoshi , Baba Yoshihiro , Fukui Yoshinori , Okamoto Isamu TITLE=Mass cytometry identifies characteristic immune cell subsets in bronchoalveolar lavage fluid from interstitial lung diseases JOURNAL=Frontiers in Immunology VOLUME=14 YEAR=2023 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1145814 DOI=10.3389/fimmu.2023.1145814 ISSN=1664-3224 ABSTRACT=

Immune cells have been implicated in interstitial lung diseases (ILDs), although their phenotypes and effector mechanisms remain poorly understood. To better understand these cells, we conducted an exploratory mass cytometry analysis of immune cell subsets in bronchoalveolar lavage fluid (BALF) from patients with idiopathic pulmonary fibrosis (IPF), connective-tissue disease (CTD)-related ILD, and sarcoidosis, using two panels including 64 markers. Among myeloid cells, we observed the expansion of CD14⁺ CD36^hi CD84^hiCCR2^– monocyte populations in IPF. These CD14⁺ CD36^hi CD84^hi CCR2^– subsets were also increased in ILDs with a progressive phenotype, particularly in a case of acute exacerbation (AEx) of IPF. Analysis of B cells revealed the presence of cells at various stages of differentiation in BALF, with a higher percentage of IgG memory B cells in CTD-ILDs and a trend toward more FCRL5⁺ B cells. These FCRL5⁺ B cells were also present in the patient with AEx-IPF and sarcoidosis with advanced lung lesions. Among T cells, we found increased levels of IL-2R⁺ TIGIT⁺ LAG3⁺ CD4⁺ T cells in IPF, increased levels of CXCR3⁺ CD226⁺ CD4⁺ T cells in sarcoidosis, and increased levels of PD1⁺ TIGIT⁺ CD57⁺ CD8⁺ T cells in CTD-ILDs. Together, these findings underscore the diverse immunopathogenesis of ILDs.