Constitutive induction of intestinal <scp>T</scp>c17 cells in the absence of hematopoietic cell‐specific <scp>MHC</scp> class II expression

Rubino, Stephen; Geddes, Kaoru; Magalhães, João G.; Streutker, Catherine; Philpott, Dana J.; Girardin, Stephen E.

doi:10.1002/eji.201243028

Cited by 8 publications

(5 citation statements)

References 46 publications

(85 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mice lacking Th17 cells or their associated cytokines are also susceptible to C. rodentium (26)(27)(28)(29). Although mechanisms of Th1 and Th17 induction after C. rodentium infection have been reported (25,28,(30)(31)(32), it is not clear whether these effector T cells are also counterregulated and controlled during and after infection.…”

mentioning

confidence: 99%

Attenuation of Intestinal Inflammation in Interleukin-10-Deficient Mice Infected with Citrobacter rodentium

Dann

Choudhury

et al. 2014

Infect Immun

View full text Add to dashboard Cite

dInterleukin-10 (IL-10) curtails immune responses to microbial infection and autoantigens and contributes to intestinal immune homeostasis, yet administration of IL-10 has not been effective at attenuating chronic intestinal inflammatory conditions, suggesting that its immune functions may be context dependent. To gain a broader understanding of the importance of IL-10 in controlling mucosal immune responses to infectious challenges, we employed the murine attaching and effacing pathogen Citrobacter rodentium, which colonizes primarily the surfaces of the cecum and colon and causes transient mucosal inflammation driven by Th17 and Th1 T helper cells. Infection induced macrophage and dendritic cell production of IL-10, which diminished antibacterial host defenses, because IL-10-deficient mice cleared infection faster than wild-type controls. In parallel, the mice had less acute infection-associated colitis and resolved it more rapidly than controls. Importantly, transient C. rodentium infection protected IL-10-deficient mice against the later development of spontaneous colitis that normally occurs with aging in these mice. Genome-wide expression studies revealed that IL-10 deficiency was associated with downregulation of proinflammatory pathways but increased expression of the anti-inflammatory cytokine IL-27 in response to infection. IL-27 was found to suppress in vitro Th17 and, to a lesser degree, Th1 differentiation independent of IL-10. Furthermore, neutralization of IL-27 resulted in more severe colitis in infected IL-10-deficient mice. Together, these findings indicate that IL-10 is dispensable for resolving C. rodentium-associated colitis and further suggest that IL-27 may be a critical factor for controlling intestinal inflammation and Th17 and Th1 development by IL-10-independent mechanisms.

show abstract

mentioning

confidence: 99%

Attenuation of Intestinal Inflammation in Interleukin-10-Deficient Mice Infected with Citrobacter rodentium

Dann

Choudhury

et al. 2014

Infect Immun

View full text Add to dashboard Cite

show abstract

“…The increased mRNA expression of Il10 and presence of Foxp3+ cells may indicate to an unsuccessful attempt of Treg cells to control the inflammatory response. Although the mouse Foxp3+ cells are regarded as Treg cells, a subset of Foxp3 expressing CD8+ cytotoxic T cells were found to be involved in early Th17 cell-mediated immune response to enteric pathogen in mice [47] . Furthermore, IL17- and IFNγ secreting Foxp3+ T cells have been demonstrated in peripheral lymph nodes and the spleen [48] .…”

Section: Discussionmentioning

confidence: 99%

Transcriptional modulation of pattern recognition receptors in chronic colitis in mice is accompanied with Th1 and Th17 response

Zheng

Morgan

Kant

et al. 2017

Biochemistry and Biophysics Reports

View full text Add to dashboard Cite

Pattern recognition receptors (PRRs) may contribute to inflammatory bowel diseases (IBD) development due to their microbial-sensing ability and the unique microenvironment in the inflamed gut. In this study, the PRR mRNA expression profile together with T cell-associated factors in the colon was examined using a chronic colitis mice model. 8–12 week old C57BL/6 mice were exposed to multiple dextran sodium sulfate (DSS) treatments interspersed with a rest period to mimic the course of chronic colitis. The clinical features and histological data were collected. The mRNA expressions of colonic PRRs, T cell-associated components were measured. Finally, the colons were scored for Foxp3+ cells. During chronic colitis, the histological data, but not the clinical manifestations demonstrated characteristic inflammatory symptoms in the distal colon. In contrast to acute colitis, the expression of all Toll-like receptors (Tlrs), except Tlr5 and Tlr9, was unaffected after repeated DSS treatments. The expression of Nod1 was decreased, while Nod2 increased. After third DSS treatment, only the expressions of Tlr3 and Tlr4 were significantly enhanced. Unlike other PRRs, decreased Tlr5 and increased Tlr9 mRNA expression persisted during the chronic colitis period. As the colitis progress, only the mRNA expression of Ifnγ and Il17 staid increased during chronic colitis, while the acute colitis-associated increase of Il23, and Il10 and Il12 was abolished. Finally, increased histological score of Foxp3+ cell in colon was found during the chronic colitis period. This study provides an expression pattern of PRRs during chronic colitis that is accompanied by a Th1- and Th17 cell-mediated immune response.

show abstract

“…This finding indicates that increased Tc17 cells are not a compensation for a loss in Th17 cell numbers. Interestingly, Th17-mediated protection against Citrobacter rodentium intestinal infections is abrogated in a bone marrow chimeric mouse model where MHC-II presentation is absent only on hematopoietic cells ( 50 ). Coincidentally, the number of Tc1 and Tc17 cells found in the gut of these mice was substantially increased.…”

Section: Discussionmentioning

confidence: 99%

MHC-II presentation by oral Langerhans cells impacts intraepithelial Tc17 abundance and Candida albicans oral infection via CD4 T cells

Bittner-Eddy,

Fischer,

Parachuru

et al. 2024

Front. Oral. Health

View full text Add to dashboard Cite

In a murine model (LCΔMHC-II) designed to abolish MHC-II expression in Langerhans cells (LCs), ∼18% of oral LCs retain MHC-II, yet oral mucosal CD4 T cells numbers are unaffected. In LCΔMHC-II mice, we now show that oral intraepithelial conventional CD8αβ T cell numbers expand 30-fold. Antibody-mediated ablation of CD4 T cells in wild-type mice also resulted in CD8αβ T cell expansion in the oral mucosa. Therefore, we hypothesize that MHC class II molecules uniquely expressed on Langerhans cells mediate the suppression of intraepithelial resident-memory CD8 T cell numbers via a CD4 T cell-dependent mechanism. The expanded oral CD8 T cells co-expressed CD69 and CD103 and the majority produced IL-17A [CD8 T cytotoxic (Tc)17 cells] with a minority expressing IFN-γ (Tc1 cells). These oral CD8 T cells showed broad T cell receptor Vβ gene usage indicating responsiveness to diverse oral antigens. Generally supporting Tc17 cells, transforming growth factor-β1 (TGF-β1) increased 4-fold in the oral mucosa. Surprisingly, blocking TGF-β1 signaling with the TGF-R1 kinase inhibitor, LY364947, did not reduce Tc17 or Tc1 numbers. Nonetheless, LY364947 increased γδ T cell numbers and decreased CD49a expression on Tc1 cells. Although IL-17A-expressing γδ T cells were reduced by 30%, LCΔMHC-II mice displayed greater resistance to Candida albicans in early stages of oral infection. These findings suggest that modulating MHC-II expression in oral LC may be an effective strategy against fungal infections at mucosal surfaces counteracted by IL-17A-dependent mechanisms.

show abstract

Constitutive induction of intestinal Tc17 cells in the absence of hematopoietic cell‐specific MHC class II expression

Cited by 8 publications

References 46 publications

Attenuation of Intestinal Inflammation in Interleukin-10-Deficient Mice Infected with Citrobacter rodentium

Attenuation of Intestinal Inflammation in Interleukin-10-Deficient Mice Infected with Citrobacter rodentium

Transcriptional modulation of pattern recognition receptors in chronic colitis in mice is accompanied with Th1 and Th17 response

MHC-II presentation by oral Langerhans cells impacts intraepithelial Tc17 abundance and Candida albicans oral infection via CD4 T cells

Contact Info

Product

Resources

About