Recent evidence suggests that the primary progressive form of multiple sclerosis (PP-MS) may present with specific immunological alterations. In this study we focused our attention on CD161, an NK and T cell marker upregulated in relapsing-remitting MS, and investigated its transcript and protein levels in blood cells from PP-MS and healthy individuals. We demonstrated transcriptional downregulation of CD161 in PP-MS and described concomitant mRNA reduction for RORgt, CCR6, CXCR6, KLRK1/NKG2D and many other markers typical of mucosa associated invariant T (MAIT) cells. Targeted multiparametric flow cytometry on fresh blood cells from an independent cohort of case-control subjects confirmed the selective loss of circulating CD8 CD161 high T cells, which consist mainly of MAIT cells, and not of CD8 CD161 int T cells in PP-MS. These data demonstrate alterations in a specific circulating immune cell subset in MS patients with progressive onset.

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The mouse vomeronasal system controls several social behaviors. Pheromones and other social cues are detected by sensory neurons in the vomeronasal organ. Stimuli activate a transduction cascade that leads to membrane potential depolarization, increase in cytosolic Ca 2+ level, and increased firing. The Ca 2+ -activated chloride channels TMEM16A and TMEM16B are co-expressed within microvilli of vomeronasal neurons, but their physiological role remains elusive. Here, we investigate the contribution of each of these channels to vomeronasal neuron firing activity by comparing wild-type and knockout mice. Performing loose-patch recordings from neurons in acute vomeronasal organ slices, we show that spontaneous activity is modified by Tmem16a knockout, indicating that TMEM16A, but not TMEM16B, is active under basal conditions. Upon exposure to diluted urine, a rich source of mouse pheromones, we observe significant changes in activity. Vomeronasal sensory neurons from Tmem16a cKO and Tmem16b KO mice show shorter interspike intervals compared to WT mice, indicating that both TMEM16A and TMEM16B modulate the firing pattern of pheromone-evoked activity in VSNs. Significance StatementVomeronasal sensory neurons express two Ca 2+ -activated chloride channels TMEM16A and TMEM16B, however their physiological role is still unclear. Using a loss of function approach, we found that TMEM16A modulates the pattern of VSN spontaneous spike activity, while TMEM16A and TMEM16B reduced the instant frequency of pheromone-evoked activity. These new findings call for a reconsideration of the patterns of the peripheral coding of sensory stimuli.