MyD88 is critically involved in immune tolerance breakdown at environmental interfaces of Foxp3-deficient mice

Rivas, Magali Noval; Koh, Yi Ting; Chen, Andrew; Nguyen, Annie; Lee, Youngho; Lawson, Greg; Chatila, Talal A.

doi:10.1172/jci40591

Cited by 51 publications

(33 citation statements)

References 49 publications

(53 reference statements)

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“…Responses of this nature have the potential to induce release of numerous inflammatory mediators that could modulate Treg migration. In support of this concept, a recent study provided evidence that the actions of Tregs were critical in suppression of MyD88-mediated inflammatory responses in organs such as the skin and gut, where commensal micro-organisms provide tonic inflammatory stimulation (35). This provides evidence that Tregs in organs at environmental interfaces act to limit inflammation initiated by innate inflammatory activation.…”

Section: Discussionmentioning

confidence: 87%

Dermal Regulatory T Cells Display Distinct Migratory Behavior That Is Modulated during Adaptive and Innate Inflammation

Chow

Mueller

Deane

et al. 2013

The Journal of Immunology

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Regulatory T cells (Tregs) are important in controlling skin inflammation, an effect dependent on their ability to home to this organ. However, little is known regarding their behavior in the skin. Here we used multiphoton imaging in Foxp3‐GFP mice to examine the behavior of endogenous Tregs in skin. While Tregs were readily detectable in the uninflamed dermis, most were non‐motile. Induction of contact sensitivity increased the proportion of motile Tregs, as well as inducing Treg recruitment. This response was significantly blunted in mice challenged with an irrelevant hapten, and by inhibition of effector cell recruitment, indicating a role for T cell‐dependent inflammation in induction of Treg migration. Moreover, induction of Treg migration was inhibited by local injection of a CCR4 antagonist, indicating a role for CCR4 in this response. Exposure of naïve mice to hapten also induced an increase in the proportion of migratory Tregs, demonstrating that innate signals can also induce Treg migration. Simultaneous examination of the migration of CD4+ effector cells and Tregs in the same region of uninflamed skin demonstrated that effector cells behaved differently, being uniformly highly migratory. These findings indicate that Treg behavior in skin differs from that of CD4+ effector cells, in that only a low proportion of Tregs are migratory under resting conditions. However, during inflammation the proportion of migratory Tregs increases, raising the possibility that this response may be important in controlling skin inflammation.

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Section: Discussionmentioning

confidence: 87%

Dermal Regulatory T Cells Display Distinct Migratory Behavior That Is Modulated during Adaptive and Innate Inflammation

Chow

Mueller

Deane

et al. 2013

The Journal of Immunology

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“…Histopathological scoring of tissue inflammation was carried out as previously described (43). Lung inflammation was scored separately for cellular infiltration around blood vessels and airways as follows: 0, no infiltrates; 1, few inflammatory cells; 2, a ring of inflammatory cells 1 cell layer deep; 3, a ring of inflammatory cells 2-4 cells deep; 4, a ring of inflammatory cells greater than 4 cells deep.…”

Section: Methodsmentioning

confidence: 99%

Itch expression by Treg cells controls Th2 inflammatory responses

Jin¹,

Park²,

Elly³

et al. 2013

J. Clin. Invest.

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“…Staining with PE-conjugated I-A b :2W1S 52-68 tetramer and enrichment using anti-PE beads were performed as described (32). For cytokine production, cells were stimulated with phorbol myristate acetate/ionomycin in media supplemented with GolgiPlug (BD Biosciences) for 5 h. For histology, each tissue was fixed with paraformaldehyde and embedded in paraffin, cut to 5-μM sections, and stained with H&E. Tissue inflammation scoring was performed in a blinded fashion using previously reported parameters (29,(45)(46)(47), which are more fully described in SI Appendix.…”

Section: Methodsmentioning

confidence: 99%

Commensal microbes drive intestinal inflammation by IL-17–producing CD4 ⁺ T cells through ICOSL and OX40L costimulation in the absence of B7-1 and B7-2

Luo¹,

Jiang²,

Chaturvedi³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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The costimulatory B7-1 (CD80)/B7-2 (CD86) molecules, along with T-cell receptor stimulation, together facilitate T-cell activation. This explains why in vivo B7 costimulation neutralization efficiently silences a variety of human autoimmune disorders. Paradoxically, however, B7 blockade also potently moderates accumulation of immune-suppressive regulatory T cells (Tregs) essential for protection against multiorgan systemic autoimmunity. Here we show that B7 deprivation in mice overrides the necessity for Tregs in averting systemic autoimmunity and inflammation in extraintestinal tissues, whereas peripherally induced Tregs retained in the absence of B7 selectively mitigate intestinal inflammation caused by Th17 effector CD4 + T cells. The need for additional immune suppression in the intestine reflects commensal microbe-driven T-cell activation through the accessory costimulation molecules ICOSL and OX40L. Eradication of commensal enteric bacteria mitigates intestinal inflammation and IL-17 production triggered by Treg depletion in B7-deficient mice, whereas re-establishing intestinal colonization with Candida albicans primes expansion of Th17 cells with commensal specificity. Thus, neutralizing B7 costimulation uncovers an essential role for Tregs in selectively averting intestinal inflammation by Th17 CD4 + T cells with commensal microbe specificity.

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MyD88 is critically involved in immune tolerance breakdown at environmental interfaces of Foxp3-deficient mice

Cited by 51 publications

References 49 publications

Dermal Regulatory T Cells Display Distinct Migratory Behavior That Is Modulated during Adaptive and Innate Inflammation

Dermal Regulatory T Cells Display Distinct Migratory Behavior That Is Modulated during Adaptive and Innate Inflammation

Itch expression by Treg cells controls Th2 inflammatory responses

Commensal microbes drive intestinal inflammation by IL-17–producing CD4 ⁺ T cells through ICOSL and OX40L costimulation in the absence of B7-1 and B7-2

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MyD88 is critically involved in immune tolerance breakdown at environmental interfaces of Foxp3-deficient mice

Cited by 51 publications

References 49 publications

Dermal Regulatory T Cells Display Distinct Migratory Behavior That Is Modulated during Adaptive and Innate Inflammation

Dermal Regulatory T Cells Display Distinct Migratory Behavior That Is Modulated during Adaptive and Innate Inflammation

Itch expression by Treg cells controls Th2 inflammatory responses

Commensal microbes drive intestinal inflammation by IL-17–producing CD4 + T cells through ICOSL and OX40L costimulation in the absence of B7-1 and B7-2

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Resources

About

Commensal microbes drive intestinal inflammation by IL-17–producing CD4 ⁺ T cells through ICOSL and OX40L costimulation in the absence of B7-1 and B7-2