Highlights d Adipose-specific Naa10p depletion prevents diet-induced obesity d Naa10p depletion increases Ucp1 expression and thermogenesis in beige adipocytes d N-terminal acetylation of Pgc1a by Naa10p suppresses thermogenic gene expression d Higher NAA10 expression correlates with human obesity

Rag-1-knockout (KO) mice are highly resistant to Listeria monocytogenes infection. The role played by the many Rag-1-dependent lymphocyte lineages was studied using a genetic approach in which each Rag-1-dependent lymphocyte lineage was eliminated one at a time. Only B cell-deficient Igh-KO mice displayed reduced bacterial load and improved survival upon Listeria infection. Listeria infection of Rag-1-KO and Il-10-KO hosts that had been adoptively transferred with wild-type marginal zone B (MZB) cells, but not follicular B cells, resulted in heightened bacterial load and increased Il-10 production in the spleen, but not the liver. This MZB cell-dependent increase in bacterial load was eliminated by anti-Il-10 mAb. In addition, Listeria infection of MZB cell-deficient Rbpj-cKO mice showed decreased bacterial load and increased survival. Whereas multiple cell types have been shown to be capable of Il-10 production, our results indicate that the MZB cell is the most dominant and relevant Il-10 source in the context of Listeria susceptibility. In marked contrast to the generally protective nature of MZB cells in defending against pathogenic infection, our results demonstrate that MZB cells play a detrimental role in Listeria infection and possibly other infections as well.

Upon adoptive transfer into histocompatible mice, naive CD8+ T cells stimulated ex vivo by TCR+IL-4 turn into long-lived functional memory cells. The liver contains a large number of so formed memory CD8+ T cells, referred to as liver memory T cells (Tlm) in the form of cell clusters. The CD62Llow expression and nonlymphoid tissue distribution of Tlm cells are similar to effector memory (Tem) cells, yet their deficient cytotoxicity and IFN-γ inducibility are unlike Tem cells. Adoptive transfer of admixtures of TCR+IL-4–activated Vβ8+ and Vβ5+ CD8+ T cells into congenic hosts reveals Tlm clusters that are composed of all Vβ5+ or Vβ8+, not mixed Vβ5+/Vβ8+ cells, indicating that Tlm clusters are formed by clonal expansion. Clonally expanded CD8+ T cell clusters are also seen in the liver of Listeria monocytogenes-immune mice. Tlm clusters closely associate with hepatic stellate cells and their formation is IL-15/IL-15R–dependent. CD62Llow TLM cells can home to the liver and secondary lymphoid tissues, remain CD62Llow, or acquire central memory (Tcm)-characteristic CD62Lhi expression. Our findings show the liver as a major site of CD8+ memory T cell growth and that Tlm cells contribute to the pool of peripheral memory cells. These previously unappreciated Tlm characteristics indicate the inadequacy of the current Tem/Tcm classification scheme and help ongoing efforts aimed at establishing a unifying memory T cell development pathway. Lastly, our finding of Tlm clusters suggests caution against interpreting focal lymphocyte infiltration in clinical settings as pathology and not normal physiology.

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