Carbonic anhydrase enzymes regulate mast cell–mediated inflammation

Henry, Everett; Sy, Chandler B.; Inclan-Rico, Juan M.; Espinosa, Vanessa; Ghanny, Saleena; Dwyer, Daniel F.; Soteropoulos, Patricia; Rivera, Amariliz; Siracusa, Mark C.

doi:10.1084/jem.20151739

Cited by 28 publications

(42 citation statements)

References 36 publications

(61 reference statements)

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“…For example, it was shown that inhibition of Car1 was sufficient to prevent mast cell responses in murine models of helminth infection and allergic inflammation. Consistent with murine models, Car1 inhibition also prevented the development of human mast cells from blood-resident progenitor cells(127). …”

Section: Innate Immunitymentioning

confidence: 60%

“…Their development into either connective tissue or mucosal mast cells is dependent on signals received from the local tissue environment (126). Our recent work suggest that the lineage commitment of peripheral progenitor cell populations to the mast cell lineage is mediated, in part, by expression of the enzyme carbonic anhydrase I (Car1)(127). For example, it was shown that inhibition of Car1 was sufficient to prevent mast cell responses in murine models of helminth infection and allergic inflammation.…”

Section: Innate Immunitymentioning

confidence: 99%

“…In these studies it was demonstrated that mast cell-deficient mice exhibit delayed clearance of Trichinella larvae(130). It was subsequently shown that interrupting mast cell developing by targeting Car1 also results in reduced protective immunity to T. spiralis (127). In addition to T. spiralis , Hepworth and colleagues demonstrated that mast cell degranulation was essential for establishing immunity to H. polygyrus and T. muris (131).…”

Section: Innate Immunitymentioning

confidence: 99%

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Type 2 Cytokine Responses: Regulating Immunity to Helminth Parasites and Allergic Inflammation

2017

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Purpose of Review It is well established that T helper type 2 (TH2) immune responses are necessary to provide protection against helminth parasites but also to promote the detrimental inflammation associated with allergies and asthma. Given the importance of type 2 immunity and inflammation, many studies have focused on better understanding the factors that regulate TH2 cell development and activation. As a result, significant progress has been made in understanding the signaling pathways and molecular events necessary to promote TH2 cell polarization. In addition to the adaptive compartment, emerging studies are better defining the innate immune pathways needed to promote TH2 cell responses. Given the recent and substantial growth of this field, the purpose of this review is to highlight recent studies defining the innate immune events that promote immunity to helminth parasites and allergic inflammation. Recent Findings Emerging studies have begun to elucidate the importance of cytokine alarmins such as thymic stromal lymphopoietin (TSLP), IL-25 (IL-17E) and IL-33 in promoting type 2 immunity and inflammation following helminth challenge or exposure to allergens. Specifically, recent reports have begun to define the complex cellular networks these alarmins activate and their contribution to type 2 immunity and inflammation. Summary Our increased understanding of the pathways that regulate type 2 cytokine-mediated immunity and inflammation have revealed novel therapeutic targets to treat both helminth infections and allergic disease states.

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Section: Innate Immunitymentioning

confidence: 60%

Section: Innate Immunitymentioning

confidence: 99%

Section: Innate Immunitymentioning

confidence: 99%

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Type 2 Cytokine Responses: Regulating Immunity to Helminth Parasites and Allergic Inflammation

2017

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“…It is known that solid tumors are featured by the tumor microenvironment, with aberrant activation of numerous immune cells28. Interestingly, CA2 and other carbonic anhydrases can cause autoimmune reaction via activating mast cells37 and plasma cells3839. Thus, the diagnostic power of CA2 on NPC has comparable evidence from other solid tumor types, and it potentially reflects the inflaming tumor microenvironment.…”

Section: Discussionmentioning

confidence: 99%

SWATH-based proteomics identified carbonic anhydrase 2 as a potential diagnosis biomarker for nasopharyngeal carcinoma

Luo

Mok

Lin

et al. 2017

Sci Rep

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Nasopharyngeal carcinoma (NPC) is a serious threat to public health, and the biomarker discovery is of urgent needs. The data-independent mode (DIA) based sequential window acquisition of all theoretical fragment-ion spectra (SWATH) mass spectrometry (MS) has been proved to be precise in protein quantitation and efficient for cancer biomarker researches. In this study, we performed the first SWATH-MS analysis comparing the NPC and normal tissues. Spike-in stable isotope labeling by amino acids in cell culture (super-SILAC) MS was used as a shotgun reference. We identified and quantified 1414 proteins across all SWATH-MS analyses. We found that SWATH-MS had a unique feature to preferentially detect proteins with smaller molecular weights than either super-SILAC MS or human proteome background. With SWATH-MS, 29 significant differentially express proteins (DEPs) were identified. Among them, carbonic anhydrase 2 (CA2) was selected for further validation per novelty, MS quality and other supporting rationale. With the tissue microarray analysis, we found that CA2 had an AUC of 0.94 in differentiating NPC from normal tissue samples. In conclusion, SWATH-MS has unique features in proteome analysis, and it leads to the identification of CA2 as a potentially new diagnostic biomarker for NPC.

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“…Unlike basophils, which have a lifespan of just a matter of hours, MCs are long-lived, surviving for weeks or months, at least in mice, producing cytokines, chemokines, and releasing pre-stored mediators (Voehringer, 2013). While the developmental pathways that govern MC differentiation and accumulation in tissues during inflammation are not fully described, recent work from Siracusa and colleagues show that MC development depends on the expression of carbonic an hydrase enzymes in MC progenitors (Henry et al , 2016). Expression of these enzymes was required for infection-induced mastocytosis during T. spiralis infection, and absence of these enzymes led to a reduction in MC-induced inflammation in the host during murine infection.…”

Section: Introductionmentioning

confidence: 99%

The role of rare innate immune cells in Type 2 immune activation against parasitic helminths

Webb

Wojno

2017

Parasitology

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Summary The complexity of helminth macroparasites is reflected in the intricate network of host cell types that participate in the Type 2 immune response needed to battle these organisms. In this context, adaptive T helper 2 cells and the Type 2 cytokines interleukin (IL)-4, IL-5, IL-9 and IL-13 have been the focus of research for years, but recent work has demonstrated that the innate immune system plays an essential role. Some innate immune cells that promote Type 2 immunity are relatively abundant, such as macrophages and eosinophils. However, we now appreciate that more rare cell types including group 2 innate lymphoid cells, basophils, mast cells and dendritic cells make significant contributions to these responses. These cells are found at low frequency but they are specialized to their roles – located at sites such as the skin, lung and gut, where the host combats helminth parasites. These cells respond rapidly and robustly to worm antigens and worm-induced damage to produce essential cytokines, chemokines, eicosanoids and histamine to activate damaged epithelium and to recruit other effectors. Thus, a greater understanding of how these cells operate is essential to understanding how the host protects itself during helminth infection.

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Carbonic anhydrase enzymes regulate mast cell–mediated inflammation

Abstract: Car enzyme inhibition prevents mast cell responses and inflammation following Trichinella spiralis infection or the induction of food allergy–like disease.

Cited by 28 publications

References 36 publications

Type 2 Cytokine Responses: Regulating Immunity to Helminth Parasites and Allergic Inflammation

Type 2 Cytokine Responses: Regulating Immunity to Helminth Parasites and Allergic Inflammation

SWATH-based proteomics identified carbonic anhydrase 2 as a potential diagnosis biomarker for nasopharyngeal carcinoma

The role of rare innate immune cells in Type 2 immune activation against parasitic helminths

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