Tenascin-C plays important roles in immunity. Toll-like receptor 4, integrin α9β1 and chemokines have already been identified as key players in executing the immune regulatory functions of tenascin-C. Tenascin-C is also found in reticular fibers in lymphoid tissues, which are major sites involved in the regulation of adaptive immunity. Did the “tool box” for reading and interpreting the immune-regulating instructions imposed by tenascins and tenascin-C co-evolve? Though the extracellular matrix is ancient, tenascins evolved relatively recently. Tenascin-like genes are first encountered in cephalochordates and urochordates, which are widely accepted as the early branching chordate lineages. Vertebrates lacking jaws like the lamprey have tenascins, but a tenascin gene that clusters in the tenascin-C clade first appears in cartilaginous fish. Adaptive immunity apparently evolved independently in jawless and jawed vertebrates, with the former using variable lymphocyte receptors for antigen recognition, and the latter using immunoglobulins. Thus, while tenascins predate the appearance of adaptive immunity, the first tenascin-C appears to have evolved in the first organisms with immunoglobulin-based adaptive immunity. While a C-X-C chemokine is present in the lamprey, C-C chemokines also appear in the first organisms with immunoglobulin-based adaptive immunity, as does the major histocompatibility complex, T-cell receptors, Toll-like receptor 4 and integrin α9β1. Given the importance of tenascin-C in inflammatory events, the co-evolution of tenascin-C and key elements of adaptive and innate immunity is suggestive of a fundamental role for this extracellular matrix glycoprotein in the immune response of jawed vertebrates.
Toll-Like Receptor 4 Dependence of Innate and Adaptive Immunity toSalmonella: Importance of the Kupffer Cell Network
