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National Institute of Environmental Health Sciences

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Publication Detail

Title: Role of ROCK2 in CD4+ cells in allergic airways responses in mice.

Authors: Kasahara, D I; Mathews, J A; Ninin, F M C; Wurmbrand, A P; Liao, J K; Shore, S A

Published In Clin Exp Allergy, (2017 Feb)

Abstract: Rho kinases (ROCKs) contribute to allergic airways disease. ROCKs also play a role in lymphocyte proliferation and migration.To determine the role of ROCK2 acting within CD4+ cells in allergic airways responses.ROCK2-haploinsufficient (ROCK2+/- ) and wild-type mice were sensitized with ovalbumin (OVA). ROCK2+/- mice then received either CD4+ cells from ROCK2-sufficient OVA TCR transgenic (OT-II) mice or saline i.v. 48 h before challenge with aerosolized OVA. Wild-type mice received saline before challenge. Allergic airways responses were measured 48 h after the last challenge. Allergic airways responses were also assessed in mice lacking ROCK2 only in CD4+ cells (ROCK2CD4Cre mice) vs. control (CD4-Cre and ROCK2flox/flox ) mice.OVA-induced increases in bronchoalveolar lavage lymphocytes, eosinophils, IL-13, IL-5, and eotaxin were reduced in ROCK2+/- vs. wild-type mice, as were airway hyperresponsiveness and mucous hypersecretion. In ROCK2+/- mice, adoptive transfer with CD4+ cells from OT-II mice restored effects of OVA on lymphocytes, eosinophils, IL-13, IL-5, and mucous hypersecretion to wild-type levels, whereas eotaxin and airway hyperresponsiveness were not affected. ROCK2 inhibitors reduced IL-13-induced release of eotaxin from airway smooth muscle (ASM), similar to effects of these inhibitors on ASM contractility. Despite the ability of adoptive transfer to restore allergic airways inflammation in ROCK2-insufficient mice, allergic inflammation was not different in ROCK2CD4Cre vs. control mice.ROCK2 contributes to allergic airways responses likely via effects within ASM cells and within non-lymphocyte cells involved in lymphocyte activation and migration into the airways.

PubMed ID: 27886408 Exiting the NIEHS site

MeSH Terms: Adoptive Transfer; Animals; Bronchoalveolar Lavage Fluid/immunology; CD4-Positive T-Lymphocytes/immunology*; CD4-Positive T-Lymphocytes/metabolism*; Disease Models, Animal; Gene Deletion; Goblet Cells/metabolism; Goblet Cells/pathology; Hypersensitivity/immunology*; Hypersensitivity/metabolism*; Hypersensitivity/pathology; Hypersensitivity/therapy; Male; Mice; Mice, Knockout; Ovalbumin/immunology; Respiratory Mucosa/immunology; Respiratory Mucosa/metabolism; Respiratory Mucosa/pathology; T-Cell Antigen Receptor Specificity/immunology; rho-Associated Kinases/genetics; rho-Associated Kinases/metabolism*

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