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

Gazdhar, Amiq; Blank, Fabian; Cesson, Valerie; Lovis, Alban; Aubert, John David; Lazor, Romain; Spertini, Francois; Wilson, Anne; Hostettler, Katrin; Nicod, Laurent P; Obregon, Carolina (2017). Human Bronchial Epithelial Cells Induce CD141/CD123/DC-SIGN/FLT3 Monocytes That Promote Allogeneic Th17 Differentiation. Frontiers in immunology, 8(447), p. 447. Frontiers Research Foundation 10.3389/fimmu.2017.00447

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Pneumology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Pneumologie (Erwachsene)
09 Interdisciplinary Units > Microscopy Imaging Center MIC
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DCR Services > Core Facility Live Cell Imaging (LCI)

UniBE Contributor:

Gazdhar, Amiq and Blank, Fabian

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1664-3224

Publisher:

Frontiers Research Foundation

Language:

English

Submitter:

Rahel Holderegger

Date Deposited:

14 Dec 2017 10:46

Last Modified:

19 Feb 2019 14:51

Publisher DOI:

10.3389/fimmu.2017.00447

PubMed ID:

28487694

Uncontrolled Keywords:

FLT3 IL-1β Th17 bronchial epithelial cell-conditioned media interleukin-17 monocyte-derived dendritic cell monocytes

BORIS DOI:

10.7892/boris.107454

URI:

https://boris.unibe.ch/id/eprint/107454

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