Human Bronchial Epithelial Cells Induce CD141/CD123/DC-SIGN/FLT3 Monocytes That Promote Allogeneic Th17 Differentiation

Abstract

Little is known about monocyte differentiation in the lung mucosal environment and about how the epithelium shapes monocyte function. We studied the role of the soluble component of bronchial epithelial cells (BECs) obtained under basal culture conditions in innate and adaptive monocyte responses. Monocytes cultured in bronchial epithelial cell-conditioned media (BEC-CM) specifically upregulate CD141, CD123, and DC-SIGN surface levels and FLT3 expression, as well as the release of IL-1β, IL-6, and IL-10. BEC-conditioned monocytes stimulate naive T cells to produce IL-17 through IL-1β mechanism and also trigger IL-10 production by memory T cells. Furthermore, monocytes cultured in an inflammatory environment induced by the cytokines IL-6, IL-8, IL-1β, IL-15, TNF-α, and GM-CSF also upregulate CD123 and DC-SIGN expression. However, only inflammatory cytokines in the epithelial environment boost the expression of CD141. Interestingly, we identified a CD141/CD123/DC-SIGN triple positive population in the bronchoalveolar lavage fluid (BALF) from patients with different inflammatory conditions, demonstrating that this monocyte population exists in vivo. The frequency of this monocyte population was significantly increased in patients with sarcoidosis, suggesting a role in inflammatory mechanisms. Overall, these data highlight the specific role that the epithelium plays in shaping monocyte responses. Therefore, the unraveling of these mechanisms contributes to the understanding of the function that the epithelium may play in vivo.

The Long Noncoding RNA MALAT1 Induces Tolerogenic Dendritic Cells and Regulatory T Cells via miR155/Dendritic Cell-Specific Intercellular Adhesion Molecule-3 Grabbing Nonintegrin/IL10 Axis

“…As a cell receptor, DC-SIGN mediates the functions of DCs and macrophages in presenting and shaping T cell immunity ( 12 , 13 ). It is involved in immunosuppressive maintenance after transplantation and during tumor growth and pathogenic infection ( 11 , 14 , 15 ).…”

“…This receptor is involved in many aspects of DCs, including pathogen recognition and antigen presenting, and is thus considered a functional hallmark of DCs. DC-SIGN mediates the functions of DCs and macrophages in presenting and shaping T cell immunity ( 9 – 13 ). Due to its immune regulatory functions, DC-SIGN is also involved in immunosuppressive maintenance after transplantation and during tumor growth and pathogenic infection ( 14 , 15 ).…”

Acute Lung injury evolution in Covid-19

“…positive for CD123, CD208, CD206, and PD-L1). Interestingly, similar phenotypes can be induced in monocytes by pulmonary epithelial cells, determining pro-inflammatory cytokine production 37 .…”

Update on Dendritic Cell-Induced Immunological and Clinical Tolerance

“…However, it has been difficult to properly identify ModDCs in vivo due to common features shared by cDCs, monocytes and macrophages. Recent data suggest that a ModDCs subset may exist in humans ( 10 – 12 , 25 , 30 ). For example, studies in steady-state conditions described a subpopulation of cells expressing CD1c + CD14 + HLA-DR + in both blood and bronchoalveolar lavage fluid (BALF) ( 10 , 18 ).…”

“…Interestingly, in non-diseased lung tissue CD1c + CD14 + populations were shown to be enriched for the gene signatures of ModDCs described in the literature, which includes the expression of ZBTB46, IRF4 , and FLT3 genes ( 10 ). During inflammation, CD1c + CD14 + cells have been reported in the BALF from sarcoidosis patients co-expressing CD141, CD123, and DC-SIGN, or in synovial fluid from rheumatoid arthritis (RA) patients and carcinomatous ascites from untreated cancer patients co-expressing CD1a, FcεRI, CD172a, and CD206 ( 11 , 12 ). These cells were enriched for the ModDC signature and functionally ModDC from ascites showed an important capacity to polarize naive T cells into Th17 cells as well as to stimulate memory CD4 T cells to produce IL-17 ( 11 ).…”