Abstract
Acquired immunity is orchestrated in various lymphoid organs, including bone marrow, thymus, spleen, and lymph nodes in humans. However, mucosa-associated lymphoid tissue (MALT) is evolutionally known to be emerged in the oldest vertebrates as an immunological tissue for acquired immunity, much earlier than the advent of lymph nodes which appeared in endotherms. Furthermore, the lymphocytes which developed in MALT are known to circulate within the limited anatomical areas. Thus, MALT is comprehended as not the structure but the immune network dedicated to local immunity. As for the skin, skin-associated lymphoid tissue (SALT) was previously postulated; however, its existence has not been proven. Our group recently showed that aggregations of dendritic cells, M2 macrophages, and high endothelial venules (HEVs) are essential components to activate effector T cells in the murine contact hypersensitivity model and termed it as inducible SALT (iSALT) since it was a transient entity that serves for acquired immunity of the skin. Furthermore, in various human skin diseases, we reported that the ectopic formation of lymphoid follicles that immunohistochemically analogous to MALT and regarded them as human counterparts of iSALT. These data raised the possibility that SALT can exist as an inducible form, namely iSALT, which shares the biological significance of MALT. In this article, we revisit the evolution of immunological organs and the related components among vertebrates to discuss the conserved functions of MALT. Furthermore, we also discuss the putative characteristics and functions of iSALT in the context of the MALT concept.
Highlights
The conceptual framework of skin-associated lymphoid tissue (SALT) was proposed by Streilein as early as 1978 [1]
Do TLSs including inducible skinassociated lymphoid tissue (iSALT) harbor local circulating lymphocytes, which belong to each TLS?
Do TLSs including iSAL T encompass the same immunological functionality?. These questions will answer whether all TLSs defined by histology-based study, including iSALT, contributes to the local immunity in contrast with lymph nodes that play pivotal roles in systemic immunity
Summary
The conceptual framework of skin-associated lymphoid tissue (SALT) was proposed by Streilein as early as 1978 [1]. This discrepancy in the definition of TLS highlights the fundamental question of whether all lymphoid follicles histopathologically analogous to lymph nodes possess local immune function, which is characterized by immune cells circulating between inductive and effector sites Research to address this question will determine whether the concept of SALT postulated by Streilein exists. CD138+ plasma cells with polyclonal IgG expression surround the lymphoid follicles [23] Histological evidence of these components suggests that MALT structures play a role in acquired immunity, similar to lymph nodes [24, 25]. Another intriguing aspect is that only endotherms form lymph nodes, Peyer’s patches, and germinal centers containing FDCs, all of which require lymphotoxin for development [11] This led us to further speculate that MALT, capsule-free lymphoid tissue, is a precursor of all SLOs, which encompasses MMC formation under certain stimuli such as inflammation. It is essential to clarify mechanistic insights of iSALT to comprehend the local immunity of the skin
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