Related Experiment Video
Updated: Jun 21, 2026
16:01
Investigating Mast Cell Secretory Granules; from Biosynthesis to Exocytosis
Published on: January 26, 2015
Mast cells down-regulate CD4+CD25+ T regulatory cell suppressor function via histamine H1 receptor interaction
Nicholas A Forward1, Suzanne J Furlong, Yongjun Yang
1Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.
Journal of Immunology (Baltimore, Md. : 1950)
|August 12, 2009
Summary
Mast cells, through histamine signaling via H1 receptors, can reduce the immune-suppressing function of regulatory T cells (Treg cells). This finding suggests a mechanism for enhancing immune responses during infections.
Area of Science:
- Immunology
- Cellular Biology
- Allergy and Inflammation Research
Background:
- Mast cells are crucial immune cells involved in both innate and adaptive immunity.
- The impact of mast cells on the function of regulatory T cells (Treg cells) remains largely unexplored.
- Treg cells play a vital role in maintaining immune homeostasis and preventing autoimmunity.
Purpose of the Study:
- To investigate the effect of mast cells on the suppressive function of Treg cells.
- To elucidate the molecular mechanisms by which mast cells influence Treg cell activity.
- To determine the role of histamine and its receptors in mast cell-mediated modulation of Treg cells.
Main Methods:
- Co-culture experiments involving murine bone marrow-derived mast cells (BMMC) and CD4(+)CD25(+) Treg cells with CD4(+)CD25(-) T responder (Tresp) cells.
- Activation of BMMC using FcepsilonR cross-linking and assessment of Treg cell suppression assays.
- Treatment with histamine, histamine receptor antagonists (loratadine for H1, famotidine for H2), and receptor agonists; analysis of CD25 and Foxp3 expression on Treg cells.
Main Results:
- Activated BMMC significantly reduced the in vitro suppressive capacity of Treg cells.
- Histamine, released by activated BMMC, was identified as a key mediator inhibiting Treg cell function via the H1 receptor.
- Histamine exposure led to decreased CD25 and Foxp3 expression in Treg cells, impairing their function.
Conclusions:
- Mast cell-derived histamine inhibits Treg cell suppressor function through H1 receptor signaling.
- This histamine-mediated inhibition may transiently decrease Treg cell activity, potentially enhancing protective immunity against microbial products.
- Targeting the histamine H1 receptor could offer therapeutic strategies in immune modulation.
Related Concept Videos
01:15Receptor Downregulation in MVBs
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...
01:24T Cell Types and Functions
When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
01:25Antiasthma Drugs: Mast Cell Stabilizers and Anti-IgE Drugs
Asthma is a chronic respiratory condition for which new therapeutic avenues, including anti-inflammatory drugs like mast cell stabilizers and anti-IgE treatments, continue to be developed.
Mast cell stabilizers, such as cromolyn (also known as sodium cromoglycate) and nedocromil (Tilade), are effective drugs in asthma management. These stabilizers hinder histamine release by skillfully obstructing the activation of mast cells and other cellular entities. Notably, they navigate this task without...
Mast cell stabilizers, such as cromolyn (also known as sodium cromoglycate) and nedocromil (Tilade), are effective drugs in asthma management. These stabilizers hinder histamine release by skillfully obstructing the activation of mast cells and other cellular entities. Notably, they navigate this task without...
01:28Acid Suppressive Drugs for Peptic Ulcer Disease: Histamine H2-Receptor Antagonists
Histamine H2 receptors, which are intricately located on the basolateral membrane of parietal cells, play a crucial role in modulating gastric acid secretion. When released from enterochromaffin-like cells, histamine engages H2 receptors, initiating the cyclic AMP (cAMP) pathway. In this pathway, adenylyl cyclase converts ATP into cAMP, elevating intracellular cAMP levels. The activation of protein kinase A follows, stimulating the proton pump. This stimulation prompts the secretion of hydrogen...
01:22T Cell Activation and Clonal Selection
T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
Naive T cells that have not yet encountered an antigen express two primary CD...
01:29Hypersensitivity Reactions: Delayed Hypersensitivity Reactions
Delayed-Type Hypersensitivity (DTH), or Type IV hypersensitivity, is a cell-mediated immune response. It occurs when T cells, rather than antibodies, mediate a reaction to specific antigens. It is characterized by a delayed onset (1-2 days) and involves the recruitment of macrophages to the inflammation site.The initiation of a DTH response begins with the sensitization of T cells. During this phase, which lasts at least 1-2 weeks, antigen-specific T cells are activated, clonally expanded, and...