CCL2/CCR2-Dependent Recruitment of Th17 Cells but Not Tc17 Cells to the Lung in a Murine Asthma Model

Abstract

Background: Interleukin (IL)-17 has been implicated in the pathogenesis of asthma and the progression of airway inflammation. Here, we used a model of allergic asthma and found that the frequencies of IL-17-secreting T helper (Th)17 and CD8 (Tc)17 cells were both significantly increased, as was the expression of the CC chemokine receptor (CCR2) on the surface of these cells. CC chemokine ligand 2 (CCL2) has been shown to mediate the activation and recruitment of inflammatory cells in asthma, which are also skewed after ovalbumin (OVA) challenge. However, the role of CCL2 on Th17 cells and Tc17 cells in asthma has not been illuminated. Methods: Mice that were sensitized and challenged with OVA received anti-CCL2 antibody (Ab; 5 μg/day intratracheally) or CCR2 antagonist (RS504393, 2 mg/kg/day intraperitoneally) prior to the challenge. Some mice received an isotype control Ab or vehicle alone. We then assessed the effects of allergic asthma and anti-CCL2 Ab or CCR2 antagonist treatment on the levels of IL-17 and CCL2, the Th17 and Tc17 cell frequencies and lung tissue inflammation. Results: We demonstrated that CCL2 and IL-17 levels and the frequency of Th17 and Tc17 cells in lung tissues and bronchoalveolar lavage fluid increased in the asthma group compared with the normal control mice. Blocking the CCL2/CCR2 axis greatly reduced the Th17 but not the Tc17 cell frequency, and revealed a suppressive effect on airway inflammation. Conclusion: These findings indicate a role for the CCL2/CCR2 axis in mediating Th17 but not Tc17 cell migration during acute allergic airway inflammation.

Years in Review: Recent Progress in Cellular Allergology

“…These results confirm earlier studies performed in murine models of allergen-induced airway disease and represent further proof of the importance of Th17 cells for the pathogenesis of allergic diseases and establish peripheral blood Th17 cell counts as an attractive monitoring tool for asthma. Very much in line with the previous study, Wang et al [11] were interested in clarifying the molecular mechanisms guiding Th17 cells to the lungs in severe asthma. Therefore, the authors studied the effects of anti-CCL2 antibodies and CCR2 antagonist on the induction of allergic asthma, the levels of IL-17 and the frequencies of CCL2 + Th17 and Tc17 cells, as well as lung inflammation.…”

“…Patients treated with high-dose FP revealed a significant reduction in CCR2 expression levels. CCR2 + T cells are known to be involved in the pathogenesis of severe asthma [11] indicating that either the effector memory pool becomes reduced or CCR2 + effector memory cells are confined to other compartments within the body. Thus, drug-induced changes in the chemokine receptor expression pattern might facilitate a better understanding of organ pathology and their amelioration in asthma [10].…”

The Involvement of Protein Kinase D in T Cell-Induced Mast Cell Activation

“…3), such as CCL2/ MCP-1, which is known to mediate the activation and recruitment of inflammatory cells and plays an important role in asthma [17]. CCL2/ MCP-1 production was also reported in BMMC activated by palmitoyl-3-cysteine-serine-lysine-4 (Pam 3 CSK 4 ), SCF or FcεRI cross-linking; however, in contrast to our findings, Murphy et al [8 ]did not find PKD to be involved in degranulation.…”

Small interfering RNA directed against microRNA‑155 delivered by a lentiviral vector attenuates asthmatic features in a mouse model of allergic asthma

“…To generate an asthmatic model (6 mice per group), mice were sensitized and challenged with ovalbumin (OVA) as previously reported (23). The mice were immunized intraperitoneally on day 0 and 14 with 100 µg OVA (S7951; Sigma-Aldrich; Merck KGaA; Darmstadt, Germany) and 1 mg aluminium hydroxide (77161; Thermo Fisher Scientific, Inc., Waltham, MA, USA) in 200 µl of 0.9% saline.…”