IL-23 and Th17 Cells Enhance Th2-Cell–mediated Eosinophilic Airway Inflammation in Mice

Interactions between CD44 and hyaluronan (HA) are crucial for recruiting leukocytes to inflamed tissues. This review summarizes findings from our studies of the roles of CD44-HA interactions in leukocyte trafficking, with a particular focus on airway T helper type 2 (Th2) cells in mouse models of acute asthma. In a mite allergen-induced model of acute asthma, intraperitoneal injection of anti-CD44 monoclonal antibodies blocked lymphocytes and eosinophils from accumulating in the lung, and suppressed both the antigen-induced increase in Th2 cytokines in the bronchoalveolar lavage fluid (BALF) and airway hyperresponsiveness (AHR). CD44 deficiency was associated with decreased mite allergen-induced Th2 cell-mediated airway inflammation and AHR in sensitized mice. Asthmatic responses to antigen-sensitized splenic CD4+ T cells transferred from CD44-deficient mice were weaker than in wild-type mice. Administration of anti-CD44 monoclonal antibodies preferentially suppressed the airway accumulation of antigen-specific Th2 cells induced by antigen challenge, without affecting Th1 and Th17 cells. Increased HA-binding ability of CD44 and expression of Neu1 sialidase were observed on antigen-specific Th2 cells compared with antigen-specific Th1 and Th17 cells. Finally, in a mouse model of acute asthma, neuraminidase 1-deficient SM/J mice exhibited a lower Th2 cytokine concentration and a lower absolute Th2 cell number in the BALF, as well as an attenuated AHR. Our findings indicate that CD44 critically contributes to the antigen challenge-induced airway accumulation of antigen-specific Th2 cells, without affecting Th1 and Th17 cells, in mice. Furthermore, neuraminidase 1 activity is necessary for the interaction between HA and CD44, and Th2 cell-mediated airway inflammation.

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Faculty Opinions recommendation of RhoA orchestrates glycolysis for TH2 cell differentiation and allergic airway inflammation.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725582447.793522709 ◽

2016 ◽

Author(s):

Alessandra Pernis ◽

Edd Ricker

Keyword(s):

Cell Differentiation ◽

Airway Inflammation ◽

Allergic Airway Inflammation ◽

Th2 Cell

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Th17 cells are associated with the Th1/Th2-cell balance during Echinococcus multilocularis infection

Molecular Medicine Reports ◽

10.3892/mmr.2014.2170 ◽

2014 ◽

Vol 10 (1) ◽

pp. 236-240 ◽

Cited By ~ 14

Author(s):

XIUMIN MA ◽

LIANG WANG ◽

HUI ZHAO ◽

NANNAN PANG ◽

FENGBO ZHANG ◽

...

Keyword(s):

Echinococcus Multilocularis ◽

Th17 Cells ◽

Th2 Cell ◽

Cell Balance

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Wogonin Attenuates Ovalbumin Antigen-Induced Neutrophilic Airway Inflammation by Inhibiting Th17 Differentiation

International Journal of Inflammation ◽

10.1155/2014/571508 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 11

Author(s):

Rie Takagi ◽

Masaaki Kawano ◽

Kazuyuki Nakagome ◽

Kumiko Hashimoto ◽

Takehiro Higashi ◽

...

Keyword(s):

T Cells ◽

Airway Inflammation ◽

Th17 Cells ◽

Allergic Airway Inflammation ◽

Naive T Cells ◽

Naïve T Cells ◽

Th17 Differentiation ◽

Kampo Extracts ◽

Human And Mouse

Allergic airway inflammation is generally considered to be a Th2-type immune response. Recent studies, however, have demonstrated that Th17-type immune responses also play important roles in this process, particularly in the pathogenesis of neutrophilic airway inflammation, a hallmark of severe asthma. We scrutinized several Kampo extracts that reportedly exhibit anti-inflammatory activity by usingin vitrodifferentiation system of human and mouse naïve T cells. We found that hange-shashin-to (HST) and oren-gedoku-to (OGT) possess inhibitory activity for Th17 responsesin vitro. Indeed, wogonin and berberine, major components common to HST and OGT, exhibit Th17-inhibitory activities in both murine and human systemsin vitro. We therefore evaluated whether wogonin suppresses OVA-induced neutrophilic airway inflammation in OVA TCR-transgenic DO11.10 mice. Consequently, oral administration of wogonin significantly improved OVA-induced neutrophilic airway inflammation. Wogonin suppressed the differentiation of naïve T cells to Th17 cells, while showing no effects on activated Th17 cells.

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Role of IL-23 and Th17 Cells in Airway Inflammation in Asthma

Immune Network ◽

10.4110/in.2010.10.1.1 ◽

2010 ◽

Vol 10 (1) ◽

pp. 1 ◽

Cited By ~ 54

Author(s):

Hiroshi Nakajima ◽

Koichi Hirose

Keyword(s):

Airway Inflammation ◽

Th17 Cells

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Antagonistic Peptides That Specifically Bind to the First and Second Extracellular Loops of CCR5 and Anti-IL-23p19 Antibody Reduce Airway Inflammation by Suppressing the IL-23/Th17 Signaling Pathway

Mediators of Inflammation ◽

10.1155/2020/1719467 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Yingli Zhang ◽

Rongrong Liang ◽

Aicen Xie ◽

Wenqian Shi ◽

Huarong Huang ◽

...

Keyword(s):

Airway Inflammation ◽

Signaling Pathway ◽

Peripheral Blood ◽

Th17 Cells ◽

Inflammatory Disorder ◽

Mrna Levels ◽

T Helper 17 ◽

Mucus Production ◽

Chronic Inflammatory Disorder ◽

Extracellular Loops

Asthma is a heterogeneous chronic inflammatory disorder of the airways with a complex etiology, which involves a variety of cells and cellular components. Therefore, the aim of the study was to investigate the effects and mechanisms of antagonistic peptides that specifically bind to the first and second extracellular loops of CCR5 (GH and HY peptides, respectively) and anti-interleukin-23 subunit p19 (anti-IL-23p19) in the airway and thereby mediate inflammation and the IL-23/T helper 17 (Th17) cell pathway in asthmatic mice. An experimental asthma model using BALB/c mice was induced by ovalbumin (OVA) and treated with peptides that are antagonistic to CCR5 or with anti-IL-23p19. The extents of the asthmatic inflammation and mucus production were assessed. In addition, bronchoalveolar lavage fluid (BALF) was collected, the cells were counted, and the IL-4 level was detected by ELISA. The IL-23/Th17 pathway-related protein and mRNA levels in the lung tissues were measured, and the positive production rates of Th17 cells in the thymus, spleen, and peripheral blood were detected. The groups treated with one of the two peptides and/or anti-IL-23p19 showed significant reductions in allergic inflammation and mucus secretion; decreased expression levels of IL-23p19, IL-23R, IL-17A and lactoferrin (LTF); and reduced proportions of Th17 cells in the thymus, spleen, and peripheral blood. Specifically, among the four treatment groups, the anti-IL-23p19 with HY peptide group exhibited the lowest positive production rate of Th17 cells. Our data also showed a significant and positive correlation between CCR5 and IL-23p19 protein expression. These findings suggest that the administration of peptides antagonistic to CCR5 and/or anti-IL-23p19 can reduce airway inflammation in asthmatic mice, most likely through inhibition of the IL-23/Th17 signaling pathway, and the HY peptide can alleviate inflammation not only through the IL-23/Th17 pathway but also through other mechanisms that result in the regulation of inflammation.

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