Iannone, Raffaella (2017) LPS-elicited TSLPR Expression Enriches a Functionally Discrete Subset of Human CD14+ CD1c+ Monocytes. [Tesi di dottorato]


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Item Type: Tesi di dottorato
Resource language: English
Title: LPS-elicited TSLPR Expression Enriches a Functionally Discrete Subset of Human CD14+ CD1c+ Monocytes
Iannone, Raffaellaraffaellaiannone@hotmail.it
Date: 11 December 2017
Number of Pages: 73
Institution: Università degli Studi di Napoli Federico II
Department: dep22
Dottorato: phd053
Ciclo di dottorato: 30
Coordinatore del Corso di dottorato:
Marone, Giannimarone@unina.it
Date: 11 December 2017
Number of Pages: 73
Keywords: TSLPR CD14 CD1c
Settori scientifico-disciplinari del MIUR: Area 06 - Scienze mediche > MED/09 - Medicina interna
Date Deposited: 21 Dec 2017 09:34
Last Modified: 02 Apr 2019 11:05
URI: http://www.fedoa.unina.it/id/eprint/12105

Collection description

Thymic stromal lymphopoietin (TSLP) is a cytokine produced mainly by epithelial cells in response to inflammatory or microbial stimuli and binds to the TSLP receptor complex, a heterodimer composed of TSLP receptor (TSLPR) and IL-7 receptor α (CD127). TSLP activates multiple immune cell subsets expressing the TSLP receptor complex and plays a role in several models of disease. Although human monocytes express TSLPR and CD127 mRNAs in response to the TLR4 agonist LPS, their responsiveness to TSLP is ill-defined. We demonstrate that TSLP enhances human CD14+ monocyte CCL17 production in response to LPS and IL-4. Surprisingly, only a subset of CD14+ CD16- monocytes (TSLPR+ mono) expresses TSLP receptor complex upon LPS stimulation in an NF-κB- and p38-dependent manner. Phenotypic, functional and transcriptomic analysis revealed specific features of TSLPR+ mono, including higher CCL17 and IL-10 production and increased expression of genes with important immune functions (i.e. GAS6, ALOX15B, FCGR2B, LAIR1). Strikingly, TSLPR+ mono express higher levels of the dendritic cell marker CD1c. This evidence led us to identify a subset of peripheral blood CD14+ CD1c+ cells that expresses the highest levels of TSLPR upon LPS stimulation. The translational relevance of these findings is highlighted by the higher expression of TSLPR and CD127 mRNAs in monocytes isolated from patients with Gram-negative sepsis compared to healthy controls. Our results emphasize a phenotypic and functional heterogeneity in an apparently homogeneous population of human CD14+ CD16- monocytes and prompt further ontogenetic and functional analysis of CD14+ CD1c+ and LPS-activated CD14+ CD1c+ TSLPR+ monocytes.


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