Generation of colonic IgA-secreting cells in the caecal patch

Masahata, Kazunori; Umemoto, Eiji; Kayama, Hisako; Kotani, Manato; Nakamura, Shota; Kurakawa, Takashi; Kikuta, Junichi; Gotoh, Kazuyoshi; Motooka, Daisuke; Sato, Shintaro; Higuchi, Tomonori; Baba, Yoshifumi; Kurosaki, Tomohiro; Kinoshita, Makoto; Shimada, Yosuke; Kimura, Taishi; Okumura, Ryu; Takeda, Akira; Tajima, Makoto; Yoshie, Osamu; Fukuzawa, Masahiro; Kiyono, Hiroshi; Fagarasan, Sidonia; Iida, Tetsuya; Ishii, Masaru; Takeda, Kiyoshi

doi:10.1038/ncomms4704

Cited by 142 publications

(145 citation statements)

References 52 publications

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“…Cecal patches have adequate ability to induce antigen-specific immunoglobulin responses as with Peyer's patches and generate IgAsecreting cells migrating to the large intestine. 27 Huge number of commensal bacteria inhabit in the cecum, because the cecum in the mouse is a major site for microbial fermentation. Given that the M-cell-dependent antigen uptake initiates an antigenspecific mucosal immune response, it is possible to speculate that the attenuated M-cell maturation may prevent excess antigen uptake and subsequent immune response, and therefore contribute to establish a mutualistic symbiosis with commensal microbiota abundantly colonizing in the cecum of mice.…”

Section: Discussionmentioning

confidence: 99%

Visualization of the entire differentiation process of murine M cells: suppression of their maturation in cecal patches

et al. 2015

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The microfold (M) cell residing in the follicle-associated epithelium is a specialized epithelial cell that initiates mucosal immune responses by sampling luminal antigens. The differentiation process of M cells remains unclear due to limitations of analytical methods. Here we found that M cells were classified into two functionally different subtypes based on the expression of Glycoprotein 2 (GP2) by newly developed image cytometric analysis. GP2-high M cells actively took up luminal microbeads, whereas GP2-negative or low cells scarcely ingested them, even though both subsets equally expressed the other M-cell signature genes, suggesting that GP2-high M cells represent functionally mature M cells. Further, the GP2-high mature M cells were abundant in Peyer's patch but sparse in the cecal patch: this was most likely due to a decrease in the nuclear translocation of RelB, a downstream transcription factor for the receptor activator of nuclear factor-κB signaling. Given that murine cecum contains a protrusion of beneficial commensals, the restriction of M-cell activity might contribute to preventing the onset of any excessive immune response to the commensals through decelerating the M-cell-dependent uptake of microorganisms.

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Section: Discussionmentioning

confidence: 99%

Visualization of the entire differentiation process of murine M cells: suppression of their maturation in cecal patches

et al. 2015

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“…A previous study showed that the active metabolites of vitamin D3 could induce CCR10 expression on terminally differentiating B cells (Shirakawa et al, 2008). In addition, a recent study has shown that DCs in the caecal patch, but not Peyer’s patches, can induce CCR10 on in vitro cultured murine B cells (Masahata et al, 2014). Although it is still unclear how LOX-1-activated DCs induce pan-mucosal homing receptor CCR10 (Kunkel et al, 2003; Lazarus et al, 2003; Shirakawa et al, 2008) on B cells, this study suggests that LOX-1 can be a novel target to enhance mucosal immunity against many microbial infections.…”

Section: Discussionmentioning

confidence: 99%

C-Type Lectin-like Receptor LOX-1 Promotes Dendritic Cell-Mediated Class-Switched B Cell Responses

Joo

Dullaers

et al. 2014

Immunity

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SUMMARY Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a pattern recognition receptor for a variety of endogenous and exogenous ligands. However, LOX-1 function in the host immune response is not fully understood. Here, we report that LOX-1 expressed on dendritic cells (DCs) and B cells promotes humoral responses. On B cells LOX-1 signaling upregulated CCR7, promoting cellular migration towards lymphoid tissues. LOX-1 signaling on DCs licensed the cells to promote B cell differentiation into class-switched plasmablasts, and led to downregulation of chemokine receptor CXCR5 and upregulation of chemokine receptor CCR10 on plasmablasts, which enabled their exit from germinal centers and migration towards local mucosa and skin. Finally, we found that targeting influenza hemagglutinin 1 (HA1) subunit to LOX-1 elicited HA1-specific protective antibody responses in rhesus macaques. Thus, LOX-1 expressed on B cells and DC cells has complementary functions to promote humoral immune responses.

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“…α4β7 and CCR10 are known to mediate PB homing to the intestines in mice (6,10,11). GI patient-enriched clusters were distinguished from each other by differences in expression of other receptors.…”

Section: Patterns Of Trafficking Receptor Expression Define Discrete mentioning

confidence: 99%

“…Studies in the mouse have implicated α4β7 and its vascular ligand mucosal vascular addressin cell adhesion molecule 1 (MAdCAM1) in IgA ASC localization and function in intestinal immunity (8); CCR10 and its mucosal chemokine ligand CCL28 in IgA PB homing to the lactating mammary gland (9) and to the intestines (10,11), especially to the colon (12,13); and CCR9 and its ligand CCL25 in small intestinal homing (10,14). In humans, studies of blood-borne PBs after intestinal rotavirus (1) or Shigella (3) infection or following experimental intestinal immunization (15,16) have shown high-level expression of intestinal trafficking receptors that target antigen-specific IgA ASCs to the intestines, where they locally produce secretory IgA at the sites of infection or antigen administration.…”

Section: Introductionmentioning

confidence: 99%

Trafficking receptor signatures define blood plasmablasts responding to tissue-specific immune challenge

Seong¹,

Lazarus²,

Sutherland³

et al. 2017

JCI Insight

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Generation of colonic IgA-secreting cells in the caecal patch

Cited by 142 publications

References 52 publications

Visualization of the entire differentiation process of murine M cells: suppression of their maturation in cecal patches

Visualization of the entire differentiation process of murine M cells: suppression of their maturation in cecal patches

C-Type Lectin-like Receptor LOX-1 Promotes Dendritic Cell-Mediated Class-Switched B Cell Responses

Trafficking receptor signatures define blood plasmablasts responding to tissue-specific immune challenge

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