CCR9+ plasmacytoid dendritic cells in the small intestine suppress development of intestinal inflammation in mice

Mizuno, Shinta; Kanai, Takanori; Mikami, Yohei; Sujino, Tomohisa; Ono, Yūichi; Hayashi, Akira; Handa, Tango; Matsumoto, Atsuhiro; Nakamoto, Nobuhiro; Matsuoka, Katsuyoshi; Hisamatsu, Tadakazu; Takaishi, Hiromasa; Hibi, Toshifumi

doi:10.1016/j.imlet.2012.05.001

Cited by 36 publications

(27 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3E). In contrast to studies by Mizuno et al 36 who reported small bowel inflammation in Rag2 −/− Ccr9 −/− recipient mice that received WT CD45RB hi CD4 + T cells, ileitis was not observed in Rag1 −/− Ccl25 −/− recipient mice after T cell transfer (see Fig., Supplemental Digital Content 2, http://links.lww.com/IBD/A471). Together, incorporating the results from the last section, these data suggest that while CCR9 expression on T cells does not modulate T cell–mediated colitis in immunodeficient hosts, expression of CCL25 in recipient mice regulates the severity of T cell–mediated colitis development.…”

Section: Resultscontrasting

confidence: 80%

“…CCR9-expressing pDCs have been reported to home to small intestinal tissues in steady state and in the setting of intestinal inflammation and can modulate immune responses in extraintestinal sites. 34–36 Mizuno et al observed that Rag2 −/− Ccr9 −/− recipient mice develop ileitis, as well as colitis, when transferred with WT CD45RB hi CD4 + T cells. 36 The authors attributed the ileitis to altered localization and function of regulatory pDCs within the small intestine of Rag2 −/− Ccr9 −/− recipient mice.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

CCL25/CCR9 Interactions Are Not Essential for Colitis Development but Are Required for Innate Immune Cell Protection from Chronic Experimental Murine Colitis

Wurbel

Bras

Ibourk

et al. 2014

Inflammatory Bowel Diseases

View full text Add to dashboard Cite

Background: The chemokine CCL25, and its receptor CCR9, constitute a unique chemokine/receptor pair, which regulates trafficking of T lymphocytes to the small intestine under physiological conditions and is an attractive target for small bowel Crohn’s disease drug development. We have previously shown that CCL25/CCR9 interactions regulate the recovery from acute dextran sulfate sodium–induced colonic inflammation. In this study, we explored whether these interactions also regulate chronic colitis development in 2 independent murine models of experimental colitis. Methods: Histological flow cytometry and qPCR analyses were performed to evaluate the role of CL25 and CCR9 in chronic colonic inflammation induced by serial exposures to dextran sulfate sodium salts or by adoptive transfer of CD45RBhi CD4+ T cell into lymphopenic mice devoid of CCL25/CCR9 interactions. Results: Chronic dextran sulfate sodium exposure results in exacerbated colitis in mice deficient for either CCR9 or CCL25 when compared with wild-type control mice. Although CCR9-deficient T cells traffic to the colon and induce severe colitis similar to wild-type T cells in the CD45RB transfer model, naive wild-type T cells induce more severe disease in recipient animals devoid of CCL25 expression. Conclusions: CCL25/CCR9 interactions are required for modulating protection against large intestinal inflammation in 2 models of chronic colitis. These data may have implications for the potential effects of disrupting CCL25/CCR9 interactions in humans in the setting of intestinal disorders including inflammatory bowel disease.

show abstract

Section: Resultscontrasting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

CCL25/CCR9 Interactions Are Not Essential for Colitis Development but Are Required for Innate Immune Cell Protection from Chronic Experimental Murine Colitis

Wurbel

Bras

Ibourk

et al. 2014

Inflammatory Bowel Diseases

View full text Add to dashboard Cite

show abstract

“…31,32 Collectively, these findings suggest that pDCs are required for initiation of DSS-induced colonic inflammation and tissue damage possibly mediated through the control of mucosal production of proinflammatory cytokines. On the other hand, Mizuno et al 39 have recently suggested that CCR9 þ pDCs in the small intestine (SI) suppress the development of murine spontaneous intestinal inflammation as CCR9 þ pDCs preferentially resided in the SI in the steady state, and Ccr9 À / À Rag-2 À / À mice developed more severe ileitis compared with Rag-2 À / À mice when these mice were adoptively transferred with CD4 þ CD45RB high T cells, although they did not assess the direct contribution …”

Section: Discussionmentioning

confidence: 98%

Crucial role of plasmacytoid dendritic cells in the development of acute colitis through the regulation of intestinal inflammation

et al. 2017

View full text Add to dashboard Cite

“…PDC contribute to peripheral T cell tolerance in transplantation(71), tumor escape(72), oral-(73) and mucosal tolerance(74). “Tolerogenic” pDC may be present in mouse gut and thymus(75–77). Such pDC may express the chemokine receptor CCR9, that is lost upon TLR triggering correlating with reduced ability to prime tolerance(75).…”

Section: Tolerancementioning

confidence: 99%

The Plasmacytoid Dendritic Cell as the Swiss Army Knife of the Immune System: Molecular Regulation of Its Multifaceted Functions

Karrich

Jachimowski

Uíttenbogaart

et al. 2014

The Journal of Immunology

View full text Add to dashboard Cite

Plasmacytoid dendritic cells (pDC) have been regarded as the “professional type I interferon producing cells” of the immune system following viral recognition that relies on the expression of Toll-like receptor (TLR)7 and TLR9. Furthermore, pDC link the innate and adaptive immune systems via cytokine production and antigen presentation. More recently their ability to induce tolerance and cytotoxicity has been added to their “immune skills”. Such broad range of actions, resembling the diverse functional features of a Swiss army knife, requires strong and prompt molecular regulation to prevent detrimental effects, including autoimmune pathogenesis or tumor escape. Over the last decades, we and others have started to unravel some aspects of the signaling pathways that regulate the various functions of human pDC. Here we review aspects of the molecular regulatory mechanisms to control pDC function in light of their multifaceted roles during immunity, autoimmunity, and cancer.

show abstract

CCR9+ plasmacytoid dendritic cells in the small intestine suppress development of intestinal inflammation in mice

Cited by 36 publications

References 18 publications

CCL25/CCR9 Interactions Are Not Essential for Colitis Development but Are Required for Innate Immune Cell Protection from Chronic Experimental Murine Colitis

CCL25/CCR9 Interactions Are Not Essential for Colitis Development but Are Required for Innate Immune Cell Protection from Chronic Experimental Murine Colitis

Crucial role of plasmacytoid dendritic cells in the development of acute colitis through the regulation of intestinal inflammation

The Plasmacytoid Dendritic Cell as the Swiss Army Knife of the Immune System: Molecular Regulation of Its Multifaceted Functions

Contact Info

Product

Resources

About