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SummaryLong intergenic noncoding RNAs (lincRNAs) regulate biological processes in health and disease. Recent findings highlight the importance of lincRNAs in regulating T cell development and function. Here, we identified a lincRNA, LINC01871, which is highly induced upon CD4+ T cell activation and is predominantly located in the cytoplasm. The anti-inflammatory cytokine TGF-¦Â was found to suppress its expression. Silencing LINC01871 led to a modest decrease in IL-2 secretion. Notably, LINC01871 expression was highly specific to NK cells and T cells in several cross-tissue single cell RNA-seq atlases. These data suggest that LINC01871 is specifically expressed in T and NK cells and may contribute to T cell-mediated immunity in humans. Graphical abstract Highlights?LINC01871 is a cytoplasmic lincRNA induced upon CD4+ T cell activation?TGF-¦Â negatively regulates LINC01871 expression?Expression of LINC01871 is restricted to effector and memory T and NK cells Immunology; Molecular biology; Cell biology

Obesity is characterized by low-grade inflammation, energy imbalance and impaired thermogenesis. The role of regulatory T cells (Treg) in inflammation-mediated maladaptive thermogenesis is not well established. Here, we find that the p38 pathway is a key regulator of T cell-mediated adipose tissue (AT) inflammation and browning. Mice with T cells specifically lacking the p38 activators MKK3/6 are protected against diet-induced obesity, leading to an improved metabolic profile, increased browning, and enhanced thermogenesis. We identify IL-35 as a driver of adipocyte thermogenic program through the ATF2/UCP1/FGF21 pathway. IL-35 limits CD8+ T cell infiltration and inflammation in AT. Interestingly, we find that IL-35 levels are reduced in visceral fat from obese patients. Mechanistically, we demonstrate that p38 controls the expression of IL-35 in human and mouse Treg cells through mTOR pathway activation. Our findings highlight p38 signaling as a molecular orchestrator of AT T cell accumulation and function. Synopsis The p38 pathway regulates T cell-mediated adipose tissue inflammation and browning via IL-35. Lack of p38 activation in T cells increases IL-35, thereby inducing thermogenesis and reducing inflammation. T cell-specific deletion of p38 activators protects against diet-induced obesity, improves metabolic profiles, and enhances browning and thermogenesis.The p38 pathway plays a pivotal role in regulating T cell-mediated adipose tissue inflammation and browning.IL-35 is a significant driver of adipocyte thermogenesis and suppression of adipose tissue inflammation.The p38 pathway controls IL-35 expression in human and mouse regulatory T cells through mTOR pathway activation. The p38 pathway regulates T cell-mediated adipose tissue inflammation and browning via IL-35. Lack of p38 activation in T cells increases IL-35, thereby inducing thermogenesis and reducing inflammation.

Memory T cells are crucial players in vertebrate adaptive immunity but their development is incompletely understood. Here, we describe a method to produce human memory-like T cells from naive human T cells in culture. Using commercially available human T-cell differentiation kits, both purified naive CD8+ T cells and purified naive CD4+ T cells were activated via T-cell receptor signaling and appropriate cytokines for several days in culture. All the T-cell activators were then removed from the medium and the cultures were continued in hypoxic condition (1% O2 atmosphere) for several more days; during this period, most of the cells died, but some survived in a quiescent state for a month. The survivors had small round cell bodies, expressed differentiation markers characteristic of memory T cells and restarted proliferation when the T-cell activators were added back. We could also induce memory-like T cells from naive human T cells without hypoxia, if we froze the activated T cells or prepared the naive T cells from chilled filter buffy coats.