Pulmonary and blood dendritic cells from sarcoidosis patients more potently induce IFNγ-producing Th1 cells compared with monocytes

Abstract

Sarcoidosis is a systemic inflammatory disease mainly affecting the lungs. The hallmark of sarcoidosis are granulomas that are surrounded by activated T cells, likely targeting the disease-inducing antigen. IFNγ-producing Th1 and Th17.1 T cells are elevated in sarcoidosis and associate with disease progression. Monocytes and dendritic cells (DCs) are antigen-presenting cells (APCs) and required for T cell activation. Several subsets of monocytes and DCs with different functions were identified in sarcoidosis. However, to what extent different monocyte and DC subsets can support activation and skewing of T cells in sarcoidosis is still unclear. In this study, we performed a transcriptional and functional side-by-side comparison of sorted monocytes and DCs from matched blood and bronchoalveolar lavage (BAL) fluid of sarcoidosis patients.Transcriptomic analysis of all subsets showed upregulation of genes related to T cell activation and antigen presentation in DCs compared with monocytes. Allogeneic T cell proliferation was higher after coculture with monocytes and DCs from blood compared with BAL and DCs induced more T cell proliferation compared with monocytes.After coculture, proliferating T cells showed high expression of the transcription factor Tbet and IFNγ production. We also identified Tbet and RORγt coexpressing T cells that mainly produced IFNγ. Our data show that DCs rather than monocytes from sarcoidosis patients have the ability to activate and polarize T cells towards Th1 and Th17.1 cells. This study provides a useful in vitro tool to better understand the contribution of monocytes and DCs to T cell activation and immunopathology in sarcoidosis.

Systemic immune response to vimentin and granuloma formation in a model of pulmonary sarcoidosis

“…Sarcoidosis patients show the presence of IFNγ and IL-17 producing cells in BAL, establishing a pathogenic role for TH1/TH17/TH17.1 CD4 T cell subsets [ 36 ]. A high level of IFNγ favors the formation of Langhans MGC, while IL-13/IL-4 cytokines facilitate foreign body MGC formation [ 37 ].…”

Treatment of Granulomatous Inflammation in Pulmonary Sarcoidosis

“…The initiation of the immune response is thought to be due to the presentation of the antigen via the MHC complex, which triggers the production of numerous cytokines and chemokines, which then attract cells of the adaptive immune response. Dendritic cells likely play an important role in the presentation of antigen and continued immune response, although there are few studies establishing the exact role of these cells [9]. The abundance of current data indicates that sarcoidosis is a highly polarized Th1 response with a predominance of CD4+ lymphocytes and fewer CD8+ lymphocytes producing interferon-gamma [10].…”

From COVID-19 to Sarcoidosis: How Similar Are These Two Diseases?

“…Different T-cell subsets have been found to be associated with different types of sarcoidosis. The count of T cells expressing both T-bet and retinoic acid receptor-related orphan receptor-γt (RoR-γt) was significantly increased in the lungs of patients with Löfgren’s syndrome (LS), a type of sarcoidosis associated with a good prognosis for clear disease ( 94 ). Additionally, a subset of T cells co-expressing CXCR3 and CCR6 was observed in the BALF and lymph nodes of non-LS patients and was associated with disease progression.…”

“…Several changes in a series of cytokine levels have been observed in sarcoidosis and SARS-CoV-2. Along with extensive IFN-γ production in the lungs of sarcoidosis patients, the expression of cytokines, including pro-inflammatory cytokines, such as TNF, IL-12, IL-18, and IL-6, and regulatory cytokines, such as TGF-β and IL-10, has been reported to be upregulated in affected tissues ( 94 ). Moreover, higher levels of IL-2, IL-4, and IL-17A were observed in the serum of sarcoidosis patients than in the serum of healthy individuals ( 80 ).…”