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Role of ROCK 2 in CD 4 + cells in allergic airways responses in mice
Author(s) -
Kasahara D. I.,
Mathews J. A.,
Ninin F. M. C.,
Wurmbrand A. P.,
Liao J. K.,
Shore S. A.
Publication year - 2017
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.12866
Subject(s) - ovalbumin , eotaxin , bronchoalveolar lavage , immunology , adoptive cell transfer , chemistry , eosinophil , immune system , medicine , lung , asthma , t cell
Summary Background Rho kinases ( ROCK s) contribute to allergic airways disease. ROCK s also play a role in lymphocyte proliferation and migration. Objective To determine the role of ROCK 2 acting within CD 4 + cells in allergic airways responses. Methods ROCK 2‐haploinsufficient ( ROCK 2 +/− ) and wild‐type mice were sensitized with ovalbumin ( OVA ). ROCK 2 +/− mice then received either CD 4 + cells from ROCK 2‐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 ROCK 2 only in CD 4 + cells ( ROCK 2 CD 4Cre mice) vs. control ( CD 4‐Cre and ROCK 2 flox/flox ) mice. Results OVA ‐induced increases in bronchoalveolar lavage lymphocytes, eosinophils, IL ‐13, IL ‐5, and eotaxin were reduced in ROCK 2 +/− vs. wild‐type mice, as were airway hyperresponsiveness and mucous hypersecretion. In ROCK 2 +/− mice, adoptive transfer with CD 4 + 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. ROCK 2 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 ROCK 2‐insufficient mice, allergic inflammation was not different in ROCK 2 CD 4Cre vs. control mice. Conclusion ROCK 2 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.