Perivascular leukocyte clusters are essential for efficient activation of effector T cells in the skin

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.

Imaging CD8+T cells during diverse viral infections

“…Additionally, the skin, like the lung, represents a sight for T cell priming outside of secondary lymphoid organs, though this has not been shown during viral infection (36). Thus, much remains to be uncovered during viral skin infections.…”

Novel insights into the role of immune cells in skin and inducible skin-associated lymphoid tissue (iSALT)

“…1a) around the post-capillary venules has been discovered in the elicitation phase of the CHS reaction [3] in a murine model for contact dermatitis. In this clustering, dDCs contact the e ector T cells, leading to their activation.…”

“…Finally, we introduce the recently proposed concept of inducible SALT (iSALT), which has yielded novel insights into the roles of dermal DCs (dDCs) and macrophages in contact allergy by clarifying the details of cellular interactions in a murine contact hypersensitivity (CHS) model [3]. e concept of iSALT sheds light on the importance of the sequential cell-cell interactions among immune cells in situ for the establishment of skin in ammation.…”

Resolvin E1 inhibits dendritic cell migration in the skin and attenuates contact hypersensitivity responses

“…CD11c-YFP mice were used for the visualization of cutaneous DCs (Lindquist et al, 2004), and the ear skin of CD11c-YFP mice were subjected to two-photon microscopy observation for intravital imaging of cutaneous DCs Natsuaki et al, 2014). 1 h after the initiation of the observation, mice were treated with vehicle, RvE1, or a BLT1 antagonist, and DC morphology and motility were observed for another 3 h. Before RvE1 and/or BLT1 antagonist treatment, cutaneous DCs exhibited active motility with polarized morphology, filopodia-and lamellipodia-like structures at the leading edge, Honda et al, 2010), we examined the effect of RvE1 on each DC subset in an FITC-induced cutaneous DC migration assay.…”

“…In acquired immunity such as contact hypersensitivity (CHS), upon uptake of foreign antigens, DCs migrate to the draining LNs (dLNs) via lymphatic vessels to establish sensitization by inducing the antigen-specific T cell differentiation (Honda et al, 2013). In elicitation, DC migration to form DC-T cell clustering is required for efficient antigen presentation in situ (Natsuaki et al, 2014). Thus, active DC motility is an essential factor for acquired immunity.…”