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- Title
Perivascular leukocyte clusters are essential for efficient activation of effector T cells in the skin.
- Authors
Natsuaki, Yohei; Egawa, Gyohei; Nakamizo, Satoshi; Ono, Sachiko; Hanakawa, Sho; Okada, Takaharu; Kusuba, Nobuhiro; Otsuka, Atsushi; Kitoh, Akihiko; Honda, Tetsuya; Nakajima, Saeko; Tsuchiya, Soken; Sugimoto, Yukihiko; Ishii, Ken J; Tsutsui, Hiroko; Yagita, Hideo; Iwakura, Yoichiro; Kubo, Masato; Ng, Lai guan; Hashimoto, Takashi
- Abstract
It remains largely unclear how antigen-presenting cells (APCs) encounter effector or memory T cells efficiently in the periphery. Here we used a mouse contact hypersensitivity (CHS) model to show that upon epicutaneous antigen challenge, dendritic cells (DCs) formed clusters with effector T cells in dermal perivascular areas to promote in situ proliferation and activation of skin T cells in a manner dependent on antigen and the integrin LFA-1. We found that DCs accumulated in perivascular areas and that DC clustering was abrogated by depletion of macrophages. Treatment with interleukin 1α (IL-1α) induced production of the chemokine CXCL2 by dermal macrophages, and DC clustering was suppressed by blockade of either the receptor for IL-1 (IL-1R) or the receptor for CXCL2 (CXCR2). Our findings suggest that the dermal leukocyte cluster is an essential structure for elicitating acquired cutaneous immunity.
- Subjects
ANTIGEN presenting cells; LEUCOCYTES; MACROPHAGE activation; T cells; CELL proliferation; CHEMOKINE receptors; LABORATORY mice; PHYSIOLOGY
- Publication
Nature Immunology, 2014, Vol 15, Issue 11, p1064
- ISSN
1529-2908
- Publication type
Article
- DOI
10.1038/ni.2992