Kensuke Ito

In 4.062 of the Tractatus, Wittgenstein repudiates the possibility of “mak[ing] ourselves understood with false propositions just as we have done up until now with true ones”. This chapter challenges this claim by distinguishing two possible cases in which people communicate truth-apt information through false propositions. The first case presents a semantic option, where false propositions become true “construed in the new way” while people aim at conveying truths, whereas the second case presents a pragmatic option, where false propositions remain false while people aim at falsehoods. Wittgenstein’s conclusion applies to the semantic, but not to the pragmatic option. The possibility of falsity-directed communication enables us to reconstruct Dummett’s argument from his analogy between truth and winning, which refutes alethic deflationism. Finally, the chapter reconciles the debate.

Sphingosine 1-phosphate plays a role in lymphocyte egress from lymphoid organs. However, it remains unclear how S1P production and secretion are regulated. We show that under inflammatory conditions, α9 integrin, which is closely associated with activated β1 integrin, and its ligand, tenascin-C, colocalize on medullary and cortical sinuses of draining lymph nodes, which is a gate for lymphocyte exit, and that inhibition of lymphocyte egress is evident by blockade of α9 integrin-mediated signaling at dLNs. Based on in vitro analysis using lymphatic endothelial cells obtained from mice embryos, we suggested the possibility that stimulation of lymphatic endothelial cells by tenascin-C enhances S1P secretion in an α9 integrin-dependent manner without affecting S1P synthesis and/or degradation. Blockade of α9 integrin-mediated signaling reduced lymphocyte egress from dLNs in several models, including experimental autoimmune encephalomyelitis, where it improved clinical scores and pathology. Therefore, manipulating α9 integrin function may offer a therapeutic strategy for treating various inflammatory disorders.