Convergent and divergent development among M cell lineages in mouse mucosal epithelium

• Published in: The Journal of immunology (1950) Vol. 187; no. 10; pp. 5277 - 5285
• Main Authors: Wang, Jing, Gusti, Veronica, Saraswati, Andrea, Lo, David D
• Format: Journal Article
• Language: English
• Published: United States 15.11.2011
• Subjects: Animals; Carrier Proteins - biosynthesis; Carrier Proteins - genetics; Cell Lineage - genetics; Cell Lineage - immunology; Gene Knock-In Techniques; Genes, Reporter - immunology; Intestinal Mucosa - cytology; Intestinal Mucosa - immunology; Intestinal Mucosa - metabolism; Mice; Mice, 129 Strain; Mice, Inbred BALB C; Mice, Knockout; Mice, Transgenic; Nasal Mucosa - cytology; Nasal Mucosa - immunology; Nasal Mucosa - metabolism; Promoter Regions, Genetic - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1102077

M cells are specialized epithelial cells mediating immune surveillance of the mucosal lumen by transepithelial delivery of Ags to underlying dendritic cells (DC). At least three M cell phenotypes are known in the airways and intestine, but their developmental relationships are unclear. We used reporter transgenic mouse strains to follow the constitutive development of M cell subsets and their acute induction by cholera toxin (CT). M cells overlying intestinal Peyer's patches (PPs), isolated lymphoid follicles, and nasal-associated lymphoid tissue are induced by distinct settings, yet show convergent phenotypes, such as expression of a peptidoglycan recognition protein-S (PGRP-S) transgene reporter. By contrast, though PP, isolated lymphoid follicle, and villous M cells are all derived from intestinal crypt stem cells, their phenotypes were clearly distinct; for example, PP M cells frequently appeared to form M cell-DC functional units, whereas villous M cells did not consistently engage underlying DC. B lymphocytes are critical to M cell function by forming a basolateral pocket and possible signaling through CD137; however, initial commitment to all M cell lineages is B lymphocyte and CD137 independent. CT causes induction of new M cells in the airway and intestine without cell division, suggesting transdifferentiation from mature epithelial cells. In contrast with intestinal PP M cells, CT-induced nasal-associated lymphoid tissue M cells appear to be generated from ciliated Foxj1(+)PGRP-S(+) cells, indicative of a possible precommitted progenitor. In summary, constitutive and inducible differentiation of M cells is toward strictly defined context-dependent phenotypes, suggesting specialized roles in surveillance of mucosal Ags.