Protective immune responses against respiratory pathogens, including influenza virus are initiated by the mucosal immune system. However, most licensed vaccines are administered parenterally and are largely ineffective at inducing mucosal immunity. The development of safe and effective mucosal vaccines has largely been hampered by the lack of a suitable mucosal adjuvant. In this study we explore a novel class of adjuvant that harness mucosal-associated invariant T (MAIT) cells. We show evidence that intranasal immunisation of MAIT cell agonists co-administered with protein, including haemagglutinin from influenza A virus induced potent humoral immunity and immunoglobulin (Ig)A production, which protected mice against infection. MAIT cell adjuvant activity was mediated by CD40L-dependent activation of dendritic cells and subsequent priming of CD4+ T follicular helper cells. In summary, we show that MAIT cells are promising vaccine targets that can be utilised as cellular adjuvants in mucosal vaccines.

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The enhanced cognitive abilities characterizing the human species result from specialized features of neurons and circuits, but the underlying molecular mechanisms remain largely unknown. Here we report that the hominid-specific gene LRRC37B encodes a novel receptor expressed in a subset of human cortical pyramidal neurons (CPNs). LRRC37B protein localizes at the axon initial segment (AIS), the specialized domain triggering action potentials. LRRC37B ectopic expression in mouse CPNs in vivo leads to reduced intrinsic excitability, a distinctive feature of some classes of human CPNs. At the molecular level, LRRC37B acts as a receptor for the secreted ligand FGF13A and interacts with the voltage gated sodium channel (VGSC) beta subunit SCN1B, thereby inhibiting the channel function of VGSC, specifically at the AIS. Electrophysiological recordings in adult human cortical slices reveals that endogenous expression of LRRC37B in human CPNs reduces neuronal excitability. LRRC37B thus acts as a species-specific modifier of human cortical neuron function, with important implications for human brain evolution and diseases.

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