Globule Leukocytes and Other Mast Cells in the Mouse Intestine

Abstract

Only 2 major mast cell (MC) subtypes are commonly recognized in the mouse: the large connective tissue mast cells (CTMCs) and the mucosal mast cells (MMCs). Interepithelial mucosal inflammatory cells, most commonly identified as globule leukocytes (GLs), represent a third MC subtype in mice, which we term interepithelial mucosal mast cells (ieMMCs). This term clearly distinguishes ieMMCs from lamina proprial MMCs (lpMMCs) while clearly communicating their common MC lineage. Both lpMMCs and ieMMCs are rare in normal mouse intestinal mucosa, but increased numbers of ieMMCs are seen as part of type 2 immune responses to intestinal helminth infections and in food allergies. Interestingly, we found that increased ieMMCs were consistently associated with decreased mucosal inflammation and damage, suggesting that they might have a role in controlling helminth-induced immunopathology. We also found that ieMMC hyperplasia can develop in the absence of helminth infections, for example, in Treg-deficient mice, Arf null mice, some nude mice, and certain graft-vs-host responses. Since tuft cell hyperplasia plays a critical role in type 2 immune responses to intestinal helminths, we looked for (but did not find) any direct relationship between ieMMC and tuft cell numbers in the intestinal mucosa. Much remains to be learned about the differing functions of ieMMCs and lpMMCs in the intestinal mucosa, but an essential step in deciphering their roles in mucosal immune responses will be to apply immunohistochemistry methods to consistently and accurately identify them in tissue sections.

Diet differentially regulates enterochromaffin cell serotonin content, density and nutrient sensitivity in the mouse small and large intestine

“…To determine what impact DIO has on EC cell density, we examined EC cell density in proximal duodenum and colon segments. Distinguishing mast cells, which also contain 5‐HT in rodents, from EC cells by labeling with Toluidine blue revealed the extremely rare occurrence of mast cells (Figure S1), which is unsurprising given the rarity and absence of mast cells across whole tissue segments seen by others 25,26 . As such, our quantification of 5‐HT‐positive EC cells was not confounded by the presence of mucosal mast cells.…”

mTOR coordinates transcriptional programs and mitochondrial metabolism of activated Treg subsets to protect tissue homeostasis

“…2d ). T H 2 inflammation is also associated with the accumulation of mucosal mast cells (MMCs) in the intestines 37 . Foxp3 Cre Mtor fl/fl mice had an increase of MCPT1 + interepithelial MMCs and MCPT4 + lamina propria MMCs in the large and small intestines (Fig.…”

“…for the presence of lesions indicative of autoimmune disease. For the identification of ieMMCs or lpMMCs, tissue sections from the small intestines and large intestines were respectively stained with primary rat anti-MCPT1 monoclonal antibody (Cat # 14-55303-82, Thermo Fisher Scientific) or goat anti-MCPT4 antibody (LS-B5958, LifeSpan Biosciences) as described previously 37 . GCs were identified by staining with anti-CD3 antibody and peanut agglutinin as described 61 .…”

The Chymase Mouse Mast Cell Protease-4 Regulates Intestinal Cytokine Expression in Mature Adult Mice Infected with Giardia intestinalis

“…In contrast, the lack of chymase/mMCP-4 significantly reduced the infiltration of mast cells in the inflamed joint in a collagen-induced arthritis model [54], and in a model of bleomycin-induced lung inflammation, the mast cell numbers were increased in the mMCP-4 −/− mice [55]. In the mouse small intestine, the submucosal mast cell counts is normally very low (<1 mast cell per 100 villi) [56], and the low numbers of submucosal mast cells are confirmed by the low numbers of mast cell protease transcriptional reads ( [44] and Lars Hellman, personal communication). During infections with Giardia and other intestinal parasites, submucosal mast cell counts increase ( [23][24][25]57,58] and current study).…”