IL-9+ IL-10+ T cells link immediate allergic response to late phase reaction

He, S.; Liu, Z.-Q.; Chen, X.; Song, Chunhua; Zhou, Lin; Ma, Wenjing; Lv, Cheng; Du, Yun; Tang, Shangguo; Yang, Ping‐Chang

doi:10.1111/j.1365-2249.2011.04394.x

Cited by 10 publications

(9 citation statements)

References 22 publications

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“…Therefore, to study bona fide T H 9 cells in vivo , IL-9 was stained against a dump gate excluding IL-17A, FoxP3 and IL-4. Consistent with a previous study (19), multiple subcutaneous ovalbumin/alum immunisations in BALB/c mice, a classic type-2 priming model that leads to formation of T H 2 cells and IgE (19), also led to generation of T H 9 cells (CD3 + CD4 + IL-4 − IL-17A − FoxP3 − IL-9 + ) that could be detected in draining lymph nodes (Fig 4a). Analysis of chemokine receptor expression on these T H 9 cells supported in vitro observations as T H 9 cells generated in this model expressed CCR3, CCR6 and CXCR3 (Fig 4b).…”

Section: Resultssupporting

confidence: 92%

“…To generate T H 9 cells under allergic conditions, BALB/c mice were immunised subcutaneously in hind flanks with 100µg type IV ovalbumin (OVA) (Sigma) in 100µL aluminium hydroxide gel (Sigma) on days 0, 3 and 7 as previously described (19). 7 days following final sensitisation, mice were administered chemokine receptor antagonists (in 250µL endotoxin-free PBS) intravenously: 250µg MCP ala/ala (scrambled peptide control) (20, 21), 100µg CCL20 6–70 (CCR6 antagonist) (21), 250µg CXCL11 4–79 (CXCR3 antagonist) (20), 250µg SB-328457 (CCR3 antagonist; Tocris Bioscience) (22) or PBS + 0.01% Tween 80 (vehicle for SB-328457).…”

Section: Methodsmentioning

confidence: 99%

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Distinct Chemokine Receptor Axes Regulate Th9 Cell Trafficking to Allergic and Autoimmune Inflammatory Sites

Kara

Comerford

Bastow

et al. 2013

The Journal of Immunology

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Migration of TH cells to peripheral sites of inflammation is essential for execution of their effector function. The recently described TH9 subset characteristically produces IL-9 and has been implicated in both allergy and autoimmunity. Despite this, the migratory properties of TH9 cells remain enigmatic. In this study, we have examined chemokine receptor usage by TH9 cells and demonstrate, in models of allergy and autoimmunity, that these cells express functional CCR3, CCR6 and CXCR3, chemokine receptors commonly associated with other, functionally opposed, effector TH subsets. Most TH9 cells that express CCR3 also express CXCR3 and CCR6 and expression of these receptors appears to account for the recruitment of TH9 cells to disparate inflammatory sites. During allergic inflammation, TH9 cells utilize CCR3 and CCR6 but not CXCR3 to home to the peritoneal cavity, whereas TH9 homing to the central nervous system (CNS) during experimental autoimmune encephalomyelitis (EAE) involves CXCR3 and CCR6 but not CCR3. These data provide the first insights into regulation of TH9 cell trafficking in allergy and autoimmunity.

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Section: Resultssupporting

confidence: 92%

Section: Methodsmentioning

confidence: 99%

Distinct Chemokine Receptor Axes Regulate Th9 Cell Trafficking to Allergic and Autoimmune Inflammatory Sites

Kara

Comerford

Bastow

et al. 2013

The Journal of Immunology

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“…The immediate hypersensitivity reaction can be followed by a T‐cell‐mediated late phase response, which occurs 12–48 h after antigen exposure and is caused by the continuous presence of antigen . During this late phase reaction, Th2 cells and intestinal epithelial cells keep producing Th2‐related cytokines such as IL‐4, IL‐5, IL‐9, and IL‐13 .…”

Section: Food Allergy Through Broken Tolerancementioning

confidence: 99%

Immunomodulating properties of protein hydrolysates for application in cow's milk allergy

Kiewiet

Gros

Neerven

et al. 2015

Pediatric Allergy Immunology

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Cow's milk proteins cause allergic symptoms in 2-3% of all infants. In these individuals, the tolerogenic state of the intestinal immune system is broken, which can lead to sensitization against antigens and eventually to allergic responses. Although a true treatment for food allergy is not available, symptoms can be avoided by providing the infants with hydrolyzed proteins. Hydrolyzed proteins are proteins that are enzymatically degraded. They lack typical allergenic IgE-binding epitopes but are also thought to play a pertinent role in other mechanisms inducing hypoallergenic effects. This review discusses the mechanisms and evidence for immunomodulating properties of cow's milk hydrolysates. Hydrolysates are found to strengthen the epithelial barrier, modulate T-cell differentiation, and decrease inflammation. Some studies suggest a role for hydrolysates in manipulating pathogen recognition receptors signaling as underlying mechanism. Peptides from hydrolysates have been shown to bind to TLR2 and TLR4 and influence cytokine production in epithelial cells and macrophages. Current insight suggests that hydrolysates may actively participate in modulating the immune responses in subjects with cow's milk allergy and those at risk to develop cow's milk allergy. However, more research is required to design effective and reproducible means to develop targeting strategies to modulate the immune response.

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“…34 It may be speculated that memory Th9 cells exist and provide immediate high levels of IL-9 upon receiving the re-stimulation. It is also of interest that He et al 48 observed an abundance of Th9 cells in the jejunum of mice developing allergic response in that tissue 48 hours following the initiation of the response. These authors suggested, therefore, that Th9 cells serve as a link between immediate and late-phase allergic response.…”

Section: Commentsmentioning

confidence: 99%

The Unique Features of Th9 Cells and their Products

Tan

Gery

2012

Crit Rev Immunol

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Although it was discovered more than two decades ago, new information concerning the biological activities of IL-9 has been provided in recent years, after the isolation of cells that selectively produce this cytokine, designated “Th9.” Th9 cells are generated in vitro by polarization, mainly by TGF-β and IL-4, during activation with the specific antigen, or with anti-CD3/CD28 antibodies. This review deals mainly with Th9 generated by the former, “physiological” mode of activation. Of particular interest is the unique production kinetics of IL-9: the cytokine is produced very rapidly, but after reaching its peak (day 3 in our studies), it declines sharply to trace levels. In addition to IL-9, Th9 cells also produce similar amounts of another cytokine, IL-10, but the production kinetics of these two cytokines are strikingly different. Antigen-activated Th9 in our studies also developed pathogenic capacity, but only during the short time period of peak IL-9 production. Interestingly, no IL-9-producing cells were detected in sites of inflammation induced by Th9, in contrast to Th1 and Th17. The unique features of Th9 cells and their products are discussed with regards to the known and assumed functions of the cytokine.

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IL-9+ IL-10+ T cells link immediate allergic response to late phase reaction

Abstract: SummaryThe mechanism underlying late-phase allergic reactions (LPR) remains incompletely understood. This study aimed to investigate the role of a newly described subset of T cells, interleukin (

Cited by 10 publications

References 22 publications

Distinct Chemokine Receptor Axes Regulate Th9 Cell Trafficking to Allergic and Autoimmune Inflammatory Sites

Distinct Chemokine Receptor Axes Regulate Th9 Cell Trafficking to Allergic and Autoimmune Inflammatory Sites

Immunomodulating properties of protein hydrolysates for application in cow's milk allergy

The Unique Features of Th9 Cells and their Products

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