Mast Cells as a Target—A Comprehensive Review of Recent Therapeutic Approaches

Baran, Joanna; Sobiepanek, Anna; Mazurkiewicz-Pisarek, Anna; Rogalska, Marta; Gryciuk, Aleksander; Kuryk, Łukasz; Abraham, Soman N.; Staniszewska, Monika

doi:10.3390/cells12081187

Cited by 15 publications

(4 citation statements)

References 103 publications

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“…Mast cells (MCs) have been identified as contributors to both chronic and acute inflammatory responses in synovium [23,24]. An increased presence of MCs within the synovium has been identified in individuals with knee OA (KOA), with a notable emphasis on those who are obese, suggesting their active role in inflammatory processes [25][26][27].…”

Section: Introductionmentioning

confidence: 99%

Association between High HbA1c Levels and Mast Cell Phenotype in the Infrapatellar Fat Pad of Patients with Knee Osteoarthritis

Tsukada,

Takata,

Aikawa

et al. 2024

IJMS

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Diabetes mellitus (DM) has been suggested as a potential risk factor for knee osteoarthritis (KOA), and its underlying mechanisms remain unclear. The infrapatellar fat pad (IPFP) contributes to OA through inflammatory mediator secretion. Mast cells’ (MCs) role in diabetic IPFP pathology is unclear. In 156 KOA patients, hemoglobin A1c (HbA1c) was stratified (HbA1c ≥ 6.5, n = 28; HbA1c < 6.5, n = 128). MC markers (TPSB2, CPA3) in IPFP were studied. Propensity-matched cohorts (n = 27 each) addressed demographic differences. MC-rich fraction (MC-RF) and MC-poor fraction (MC-PF) were isolated, comparing MC markers and genes elevated in diabetic skin-derived MC (PAXIP1, ARG1, HAS1, IL3RA). TPSB2 and CPA3 expression were significantly higher in HbA1c ≥ 6.5 vs. <6.5, both before and after matching. MC-RF showed higher TPSB2 and CPA3 expression than MC-PF in both groups. In the HbA1c ≥ 6.5 group, PAXIP1 and ARG1 expression were significantly higher in the MC-RF than MC-PF. However, no statistical difference in the evaluated genes was detected between the High and Normal groups in the MC-RF. Elevated TPSB2 and CPA3 levels in the IPFP of high HbA1c patients likely reflect higher numbers of MCs in the IPFP, though no difference was found in MC-specific markers on a cell-to-cell basis, as shown in the MC-RF comparison. These findings deepen our understanding of the intricate interplay between diabetes and KOA, guiding targeted therapeutic interventions.

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Section: Introductionmentioning

confidence: 99%

Association between High HbA1c Levels and Mast Cell Phenotype in the Infrapatellar Fat Pad of Patients with Knee Osteoarthritis

Tsukada,

Takata,

Aikawa

et al. 2024

IJMS

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“…Mast cell activation is implicated in a diverse range of allergic disorders and innate immune processes ( 1 ). FcɛRI-IgE binding is perhaps one of the most well-known pathways for mast cell activation.…”

Section: Introductionmentioning

confidence: 99%

Functional human skin explants as tools for assessing mast cell activation and inhibition

Villanueva,

Barksdale,

Owolabi

et al. 2024

Front. Allergy

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Mast cells are activated through a variety of different receptors to release preformed granules and mediators synthesized de novo. However, the physiology and function of mast cells are not fully understood. Traditional studies of mast cell activation in humans have utilized cultures of tissue-derived mast cells including CD34+ progenitor cells or well-characterized commercially available cell lines. One limitation of these methods is that mast cells are no longer in a natural state. Therefore, their applicability to human skin disorders may be limited. Human skin explant models have been utilized to investigate the short-term effects of cell mediators, drugs, and irritants on skin while avoiding the ethical concerns surrounding in vivo stimulation studies with non-approved agents. Nonetheless, few studies have utilized intact human tissue to study mast cell degranulation. This “Methods” paper describes the development and application of an intact skin explant model to study human mast cell activation. In this manuscript, we share our protocol for setting up ex vivo human skin explants and describe the results of stimulation experiments and techniques to minimize trauma-induced histamine release. Skin explants were generated using de-identified, full-thickness, non-diseased skin specimens from plastic and reconstructive surgeries. Results were reproducible and demonstrated FcɛRI- and MRGPRX2-induced mediator release which was inhibited with the use of a BTK inhibitor and QWF, respectively. Thus, this explant model provides a quick and accessible method of assessing human skin mast cell activation and inhibition.

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“…Mast cells play a crucial role in the maintenance of many physiological functions, such as vasodilation, homeostasis, tissue remodeling, angiogenesis, activation, mediator release, and the development and amplification of the inflammatory response and antimicrobial defense. However, the mechanisms of immunological interactions are still not fully understood [ 11 , 12 , 13 , 14 , 15 , 16 , 17 ]. At the same time, MCs are involved in the pathophysiology of multiple diseases including allergies, asthma, cardiovascular diseases, pulmonary fibrosis, osteoporosis, autoimmune arthritis, multiple sclerosis, mast cell activation syndromes, neoplastic diseases, inflammatory bowel syndrome, and inflammatory bowel disease (IBD) [ 14 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

IL-10 Modulates the Expression and Activation of Pattern Recognition Receptors in Mast Cells

Riquelme-Neira

Walker-Vergara

Fernández-Blanco

et al. 2023

IJMS

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Mast cells (MCs) are involved in several immune-related responses, including those in bacterial infections, autoimmune diseases, inflammatory bowel diseases, and cancer, among others. MCs identify microorganisms by pattern recognition receptors (PRRs), activating a secretory response. Interleukin (IL)-10 has been described as an important modulator of MC responses; however, its role in PRR-mediated activation of MC is not fully understood. We analyzed the activation of TLR2, TLR4, TLR7 and Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) in mucosal-like MCs (MLMCs) and peritoneum-derived cultured MCs (PCMCs) from IL-10−/− and wild-type (WT) mice. IL-10−/− mice showed a reduced expression of TLR4 and NOD2 at week 6 and TLR7 at week 20 in MLMC. In MLMC and PCMC, TLR2 activation induced a reduced secretion of IL-6 and TNFα in IL-10−/− MCs. TLR4- and TLR7-mediated secretion of IL-6 and TNFα was not detected in PCMCs. Finally, no cytokine release was induced by NOD2 ligand, and responses to TLR2 and TLR4 were lower in MCs at 20 weeks. These findings indicate that PRR activation in MCs depends on the phenotype, ligand, age, and IL-10.

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Mast Cells as a Target—A Comprehensive Review of Recent Therapeutic Approaches

Cited by 15 publications

References 103 publications

Association between High HbA1c Levels and Mast Cell Phenotype in the Infrapatellar Fat Pad of Patients with Knee Osteoarthritis

Association between High HbA1c Levels and Mast Cell Phenotype in the Infrapatellar Fat Pad of Patients with Knee Osteoarthritis

Functional human skin explants as tools for assessing mast cell activation and inhibition

IL-10 Modulates the Expression and Activation of Pattern Recognition Receptors in Mast Cells

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