Memory CD8+ T cells in the immune system are responsible for the removal of external Ags for a long period of time to protect against re-infection. Naïve to memory CD8+ T cell differentiation and memory CD8+ T cell maintenance require many different factors including local environmental factors. Thus, it has been suggested that the migration of memory CD8+ T cells into specific microenvironments alters their longevity and functions. In this review, we have summarized the subsets of memory CD8+ T cells based on their migratory capacities and described the niche hypothesis for their survival. In addition, the basic roles of CCR7 in conjunction with the migration of memory CD8+ T cells and recent understandings of their survival niches have been introduced. Finally, the applications of altering CCR7 signaling have been discussed.

Peroxisome proliferator-activated receptor γ (PPARγ) is the master regulator of adipocyte differentiation and is closely linked to the development of obesity. Despite great progress in elucidating the transcriptional network of PPARγ, epigenetic regulation of this pathway by histone modification remains elusive. Here, we found that CDK2-associated cullin 1 (CACUL1), identified as a novel SIRT1 interacting protein, directly bound to PPARγ through the co-repressor nuclear receptor (CoRNR) box 2 and repressed the transcriptional activity and adipogenic potential of PPARγ. Upon CACUL1 depletion, less SIRT1 and more LSD1 were recruited to the PPARγ-responsive gene promoter, leading to increased histone H3K9 acetylation, decreased H3K9 methylation, and PPARγ activation during adipogenesis in 3T3-L1 cells. These findings were reversed upon fasting or resveratrol treatment. Further, gene expression profiling using RNA sequencing supported the repressive role of CACUL1 in PPARγ activation and fat accumulation. Finally, we confirmed CACUL1 function in human adipose-derived stem cells. Overall, our data suggest that CACUL1 tightly regulates PPARγ signaling through the mutual opposition between SIRT1 and LSD1, providing insight into its potential use for anti-obesity treatment.

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Memory T cells, which are generated after the primary immune response to cognate antigens, possess unique features compared to naïve or effector T cells. These memory T cells are maintained for a long period of time and robustly reactivate in lymphoid or peripheral tissues where they re-encounter antigens. Environments surrounding memory T cells are importantly involved in the process of the maintenance and reactivation of these T cells. Although memory T cells are generally believed to be formed in response to acute infections, the pathogenesis and persistence of chronic inflammatory diseases, including allergic diseases, are also related to the effector functions of memory CD4 T cells. Thus, the factors involved in the homeostasis of allergen-specific memory CD4 T cells need to be understood to surmount these diseases. Here, we review the characteristics of allergen-specific memory CD4 T cells in allergic diseases and the importance of extrinsic factors for the homeostasis and reactivation of these T cells in the view of mediating persistence, recurrence, and aggravation of allergic diseases. Overall, this review provides a better understanding of memory CD4 T cells to devise effective therapeutic strategies for refractory chronic inflammatory diseases.

Memory T (T M ) cells play an important role in the long-term defense against pathogen reinvasion. However, it is still unclear how these cells receive the crucial signals necessary for their longevity and homeostatic turnover. To understand how T M cells receive these signals, we infected mice with lymphocytic choriomeningitis virus (LCMV) and examined the expression sites of neural cadherin (N-cadherin) by immunofluorescence microscopy. We found that N-cadherin was expressed in the surroundings of the white pulps of the spleen and medulla of lymph nodes (LNs). Moreover, T M cells expressing high levels of killer cell lectin-like receptor G1 (KLRG1), a ligand of N-cadherin, were co-localized with N-cadherin + cells in the spleen but not in LNs. We then blocked N-cadherin in vivo to investigate whether it regulates the formation or function of T M cells. The numbers of CD127 hi CD62L hi T M cells in the spleen of memory P14 chimeric mice declined when N-cadherin was blocked during the contraction phase, without functional impairment of these cells. In addition, when CD127 lo KLRG1 hi T M cells were adoptively transferred into anti-N-cadherin-treated mice compared with control mice, the number of these cells was reduced in the bone marrow and LNs, with out functional loss. Taken together, our results suggest that N-cadherin participates in the development of CD127 hi CD62L hi T M cells and homing of CD127 lo KLRG1 hi T M cells to lymphoid organs.