Lymphocytes that produce IL-17 can confer protective immunity during infections by pathogens, yet their involvement in inflammatory diseases is a subject of debate. Although these cells may perpetuate inflammation, resulting in tissue damage, they are also capable of contributing directly or indirectly to tissue repair, thus necessitating more detailed investigation. Mucosal-Associated-Invariant-T (MAIT) cells are innate-like T cells, acquiring a type III phenotype in the thymus. Here, we dissected the role of MAIT cells in vivo using a spontaneous colitis model in a genetically diverse mouse strain.

Multiparameter spectral flow cytometry and scRNAseq were used to characterize MAIT and immune cell dynamics and transcriptomic signatures respectively, in the collaborative-cross strain, CC011/Unc and CC011/Unc- Traj33 -/- .

In contrast to many conventional mouse laboratory strains, the CC011 strain harbors a high baseline population of MAIT cells. We observed an age-related increase in colonic MAIT cells, Th17 cells, regulatory T cells, and neutrophils, which paralleled the development of spontaneous colitis. This progression manifested histological traits reminiscent of human IBD. The transcriptomic analysis of colonic MAIT cells from CC011 revealed an activation profile consistent with an inflammatory milieu, marked by an enhanced type-III response. Notably, IL-17A was abundantly secreted by MAIT cells in the colons of afflicted mice. Conversely, in the MAIT cell-deficient CC011-Traj33-/- mice, there was a notable absence of significant colonic histopathology. Furthermore, myeloperoxidase staining indicated a substantial decrease in colonic neutrophils.

Our findings suggest that MAIT cells play a pivotal role in modulating the severity of intestinal pathology, potentially orchestrating the inflammatory process by driving the accumulation of neutrophils within the colonic environment.

Lymphoglandular complexes (LGCs) are lymphoid nodules containing intestinal mucosa, present in close apposition to muscularis mucosae or submucosa. Rarely, colorectal adenomas involve submucosal LGCs, simulating invasive adenocarcinoma with associated submucosal lymphoid aggregates, and presenting a diagnostic pitfall. We aimed to identify distinctive histologic features between submucosal LGCs and true invasion. Seven adenomas (tubular/tubulovillous adenomas [n=6], including 4 with high-grade dysplasia and 1 with focal intramucosal adenocarcinoma, and sessile serrated adenoma [n=1]) were in the right (n=5) and left colon (n=2). Seven adenocarcinomas were in the right (n=3), left (n=2), and rectum/rectosigmoid colon (n=2). Adenomatous glands involving submucosal LGCs were invested in lamina propria, showed continuity with surface adenoma, were well rounded and contained within lymphoid tissue, and predominantly lacked classic features of "pseudoinvasion." One case showed a herniation pattern carrying muscularis mucosae. Adenocarcinomas had at least one of the following features: infiltrating single cells/small clusters (n=5), poorly formed, fused, and irregular glands (n=2), solid tumor nests (n=1), desmoplastic reaction (n=5), intraluminal necrosis (n=3), or lymphovascular invasion (n=1). In contrast, no adenoma had these features. Adenocarcinomas showed no herniation, but connection to surface tumor (n=5) was seen. Five invasive adenocarcinomas extended into the submucosa beyond the lymphoid aggregate. In conclusion, adenomas involving LGCs are a rare, clinicopathologically distinct form of pseudoinvasion that mimics invasive adenocarcinoma; histologic features that distinguish them are a well-rounded contour contained within the lymphoid tissue, and lack of infiltrating single cells/small clusters, poorly formed, fused, and irregular glands, solid tumor nests, desmoplastic reaction, and lymphovascular invasion.

Gut-associated lymphoid tissue (GALT) in the large intestine was characterized in 12 calves (10 to 84 days old) obtained at necropsy (7, group A) or healthy animals (5, group B). Patches of mucosal lymphoid follicles were in all calves at ileocecal entrances (ICE), 23-42 cm distal to the ICE in the proximal loop of the ascending colon (proximal colon [PC] patch), and in the terminal rectum. PC patches varied from 8 to 30 cm in length. Solitary lymphoid follicles were found in the cecum of three calves, between the ileocecal entrances and the PC patch in four calves, adjacent to the PC patch in all calves, and in the ampulla recti. GALT occupied 7.8% of the large intestinal wall in animals of group A: 0.6% at the ileocecal entrance, 4.8% in the proximal colon, and 2.4% in the rectum. There were two different types of mucosal lymphoid follicles in group B: propria nodules with lymphoid follicles predominantly in the lamina propria, and lymphoglandular complexes with lymphoid follicles in the submucosa. In three 3-, 6-, and 7-day-old, germfree calves, distinct follicle-associated epithelium covered propria nodules and covering folds in depths of the lymphoglandular complexes; it was characterized by numerous intraepithelial cells and lack of goblet cells.

The structure and distribution of lymphoglandular complexes of the colon are described. The cellular composition of these complexes, as detailed by immunohistochemistry and electron microscopy, suggests that they are sites of antigen processing. Variations in structure and in the number of complexes that are found in certain colonic diseases are documented.

The presence of misplaced mucosal epithelium was studied in the colectomy specimens from 30 patients with Crohn's disease, 30 patients with ulcerative colitis, 15 patients with ulcerative colitis complicated by carcinoma and 30 patients with non-colitic colorectal carcinoma. Misplaced epithelium was present in 21 (70%) of the resection specimens with Crohn's disease, 20 (66.7%) with ulcerative colitis and 12 (80%) with ulcerative colitis complicated by carcinoma. None of the specimens with non-colitic colorectal adenocarcinoma showed misplaced foci of epithelium. Two pathogenetic mechanisms for epithelial misplacement are proposed: (1) the effects of mucosal inflammation and repair; and (2) muscular abnormalities in inflammatory bowel disease. The proposed mechanisms and patterns of epithelial misplacement are discussed and illustrated. The importance of its recognition is emphasized because, when associated with mucosal dysplasia, difficulties in interpretation arise in distinguishing it from 'early' invasive adenocarcinoma. Epithelial misplacement is common in patients with longstanding ulcerative colitis and may be a factor in increasing the significance of pre-existing mucosal dysplasia and promoting the development of adenocarcinoma. This may explain the unusual growth pattern encountered in ulcerative colitis, of submucosal cancer underlying a flat, non-dysplastic mucosa.

Colectomy specimens from 62 patients (22 with ulcerative colitis, 20 with Crohn's disease of the colon, and 20 with invasive adenocarcinoma [without inflammatory bowel disease]) were reviewed for the presence of ectopic colonic mucosa. One or more foci of ectopic colonic mucosa were found in 16 of the 22 specimens (72 per cent) with ulcerative colitis and in 11 of the 20 specimens (55 per cent) with Crohn's disease of the colon. None of the 20 specimens having adenocarcinoma (without chronic inflammatory bowel disease) had ectopic colonic epithelium. The presence of ectopic colonic mucosa was found to be dependent on the age of the patients (more frequent among younger patients) and on the number of sections per specimen. One adenocarcinoma in a case of long-standing ulcerative colitis had apparently originated in ectopic colonic mucosa.

Occasionally in cases of porcine intestinal adenomatosis (PIA) epithelial dysplasia is seen with infiltration of the epithelium into underlying tissues and spread, via the lymphatics, to drainage lymph nodes. The intracellular bacterium Campylobacter sputorum subspecies mucosalis, associated with PIA, can be demonstrated in the epithelial cells of the metastases. This dysplasia and infiltration appears to be related to surface damage and inflammation.

In this study of 454 colorectal carcinoma colectomy specimens, (289 were associated with and 165 were unassociated with schistosomiasis. Schistosome infestation was found to play an etiologic role in bowel malignancy in patients having diffuse involvement of the large intestine and a history of ten years or more of colitic symptoms. Diminutive polyps, pseudopolyps, ectopically proliferating glands, disintegrated muscularis mucosae, denudation, and multicentric carcinoma were frequently encountered in the schistosomiasis-associated (SA) group, whereas papillary and adenomatous polyps were most common in the schistosomiasis nonassociated (SN) group. Pseudopolyposis, ectopically regenerating glands, and multicentricity are thought to be predisposing factors in the development of colorectal cancer. This sequence of events is analogous to the development of carcinoma in ulcerative colitis.

Grossly visible glands were found in the submucosa of the large intestine of five pigs with dysentery. Some were cystic, some were filled with necrotic debris and some had perforated the serosal surface. The mucosa of the large intestine of all pigs had areas of acute catarrhal inflammation with haemorrhage and focal sloughing of the surface epithelium. Although very distinctive and analogous in most respects to collitis cystica profunda, it was felt that the cystic and hypertrophic glands were a secondary finding and represented involvement of glandular elements present in normal animals. Anaerobic vibrio were recovered from three pigs, but the significance of these isolates is unknown.

This survey has revealed further close similarities between the pathology of certain colonic diseases in humans and primates. The changes taking place in acute inflammations of varying severity confined to the lamina propria are virtually identical as are those seen in the healing process. In primates chronic inflammatory processes caused by protozoa resemble those in humans very closely. Microherniation of mucosal glands through the muscularis mucosae were found in a wide range of species. Evidence pointed to such herniations playing an important role in the spread of inflammatory diseases from the lamina propria into the submucosa by affording the aetiological agent access through the muscularis mucosae. No case of adenocarcinoma was found in this survey and the cause for the striking difference in incidence of this disease in human and primate colons is discussed.

A case of colitis cystica superficialis is described in a Barbary ape. Early mucosal herniations through the muscularis mucosae were identified, suggesting a possible relationship between this condition and colitis cystica profunda.

Herniations of the mucosa through the colonic muscularis mucosae are described in apes and monkeys suffering from inflammatory disease of the colon as well as in apparently normal animals. Submucosal lymphoid nodules, causing discontinuity or splaying of the overlying muscularis mucosae were seen in profusion in normal colons. Evidence pointed to the fully developed herniations evolving therefrom by means of extrusion of the mucosa and that such extrusion resulted from or was hastened by contraction or hypertonicity of the colonic musculature.

The lymphoid tissue of the normal colon is compared with that of colons with diverticular disease. Colons with diverticular disease show a significant increase in the number of lymphoid nodules in areas not containing diverticula. Lymphoid-glandular complexes of the colon were studied in relation to diverticular disease. It is suggested that the lymphoid nodules and the lymphoid-glandular complexes of the colon constitute weak points in the bowel wall and may play a part in the pathogenesis of diverticula.

A study of lymphoid-glandular complexes of the large bowel has been undertaken. Sections from 1924 surgical colectomy and proctocolectomy specimens were examined, and lymphoid-glandular complexes were observed in 231. It has been shown that they are distributed throughout the large bowel and occur in all age groups and in normal and disease states. An analogy has been drawn between them, the palatine tonsils, and the bursa of Fabricius. It is concluded that the lymphoid-glandular complex is, most probably, a normal structural entity of the large bowel and that it acts as a local receptor of antigenic material for future immune recognition. It is suggested that microbursa rather than lymphoid-glandular complex is more apt name for this structure.