Biology subjects

Rönnberg, E.

Publications and source records attributed to Rönnberg, E..

2 recordsLinked to original sources

bioRxiv2021

Immunoprofiling reveals novel mast cell receptors and a continuous nature of human lung mast cell heterogeneity

BackgroundImmunohistochemical analysis of granule-associated proteases have revealed that human lungs mast cells constitute a heterogeneous population of cells, with distinct subpopulations identified. However, a systematic and comprehensive analysis of cell surface markers to study human lung mast cell heterogeneity is yet to be performed. MethodsHuman lung mast cells were obtained from lung lobectomies and the expression of 332 cell surface markers were analyzed using flow cytometry and the LEGENDScreen kit. Markers that exhibited a high variance were selected for additional analyses to reveal whether they correlated and if discrete mast cell subpopulations were discernable. ResultsWe identified expression of 102 surface markers on human lung mast cells. Several markers showed a high continuous variation of expression within the mast cell population. Six of these markers correlated: SUSD2, CD49a, CD326, CD34, CD66 and HLA-DR. The expression of these markers also correlated to the size and granularity of the mast cells. However, no marker produced an expression profile consistent with a bi- or multimodal distribution. ConclusionsLEGENDScreen analysis identified more than 100 cell surface markers on mast cells, out of which 23 have to our knowledge not previously described on human mast cells. Several of the newly described markers are known to be involved in sensing the microenvironment, and their identification can shed new light on mast cell functions. The exhaustive expression profiling of the 332 surface markers failed to detect distinct mast cell subpopulations. Instead, we demonstrate a continuous nature of human lung mast cell heterogeneity.

immunology↗

bioRxiv2018

Divergent effects of acute and prolonged interleukin 33 exposure onmast cell IgE-mediated functions

BackgroundEpithelial cytokines, including IL-33 and TSLP, have attracted interest because of their roles in chronic allergic inflammation-related conditions such as asthma. Mast cells are one of the major targets of IL-33, to which they respond by secreting cytokines. Most studies performed thus far have investigated the acute effects of IL-33 on mast cells.\n\nObjectiveThe objective of this study is to investigate how acute versus prolonged exposure of human mast cells to IL-33 and TSLP affects mediator synthesis and IgE-mediated activation.\n\nMethodsHuman lung mast cells (HLMCs), cord blood-derived mast cells (CBMCs), and the ROSA mast cell line were used for this study. Surface receptor expression and the levels of mediators were measured after treatment with IL-33 and/or TSLP.\n\nResultsIL-33 induced the acute release of cytokines. Prolonged exposure to IL-33 increased while TSLP reduced intracellular levels of tryptase. Acute IL-33 treatment strongly potentiated IgE-mediated activation. In contrast, four days of exposure to IL-33 decreased IgE-mediated activation, an effect that was accompanied by a reduction in Fc{varepsilon}RI expression.\n\nConclusion & Clinical RelevanceWe show that IL-33 plays dual roles for mast cell functions. The acute effect includes cytokine release and the potentiation of IgE-mediated degranulation, whereas prolonged exposure to IL-33 reduces IgE-mediated activation. We conclude that mast cells act quickly in response to the alarmin IL-33 to initiate an acute inflammatory response, whereas extended exposure to IL-33 during prolonged inflammation reduces IgE-mediated responses. This negative feedback effect suggests the presence of a novel IL-33 mediated regulatory pathway that modulates IgE-induced human mast cell responses.

immunology↗