Proposal of inducible skin-associated lymphoid tissue (iSALT).

In the 1980s, Streilein et al. introduced the term 'skinassociated lymphoid tissue (SALT)' based on observations that revealed the existence of T cells and dendritic cells (DCs) in the skin and that T cells are activated in the skin draining lymph nodes. However, in the perspective of SALT, it remains still unclear whether and how cellular components in the skin interact with each other. In addition, whether the T-cell activation occurs in the skin in situ has also been unrevealed. With the close observation of a skin specimen obtained from a patient with contact dermatitis, we discovered that dermal DCs (dDCs) clustered and closely attached to T cells. Thus, we hypothesized that this clustering might be essential for the establishment of the dermatitis and the T-cell activation in situ. Through the detailed examination of the elicitation phase of contact hypersensitivity as a murine model of contact dermatitis, we demonstrated the formation of sequential leukocyte clusters at the postcapillary venules. The clusters include perivascular macrophages that are activated by IL-1a produced by keratinocytes and dDCs that are attracted by these macrophages through CXCL2 signalling, both of which are essential for the efficient activation of memory T cells in situ. The structure does not exist in the steady state, but is 'induced' in response to local inflammatory conditions. Herein, we propose that this structure to be termed as 'inducible SALT (iSALT)'.