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Inflammation promotes gut polyposis Peutz–Jeghers Syndrome (PJS) causes benign polyps in the gut and a higher risk of several cancers caused by mutations in the tumor suppressor gene STK11 , which encodes liver kinase B1 (LKB1). LKB1's role in this disease is thought to be related to its tumor suppressor function. Now, Poffenberger et al. show that the T cell–specific heterozygous deletion of Stk11 is sufficient to reproduce PJS symptoms in mice (see the Perspective by Hollstein and Shaw). Polyps in mice and humans are characterized by immune cell infiltration, enhanced STAT3 signaling, and increased levels of inflammatory cytokines such as interleukin-6 (IL-6). Targeting STAT3 signaling, IL-6, or T cells ameliorated the polyps, suggesting potential therapies for this disease. Science , this issue p. 406 ; see also p. 332

Mycobacterium tuberculosis ( Mtb ) is one of the most ancient human pathogens, yet the exact mechanism(s) of host defense against Mtb remains unclear. Although one-third of the world’s population is chronically infected with Mtb , only 5 to 10% develop active disease. This indicates that, in addition to resistance mechanisms that control bacterial burden, the host has also evolved strategies to tolerate the presence of Mtb to limit disease severity. We identify mitochondrial cyclophilin D (CypD) as a critical checkpoint of T cell metabolism that controls the expansion of activated T cells. Although loss of CypD function in T cells led to enhanced Mtb antigen–specific T cell responses, this increased T cell response had no impact on bacterial burden. Rather, mice containing CypD-deficient T cells exhibited substantially compromised disease tolerance and succumbed to Mtb infection. This study establishes a mechanistic link between T cell–mediated immunity and disease tolerance during Mtb infection.

An enzyme complex coordinates metabolism and nucleotide production to fuel cell growth [Also see Reports by Ben-Sahra et al. and French et al. ]