Highlights d Bhlhe40 is required for Trm cell and TIL fitness and function d Bhlhe40 is critical for TIL reinvigoration following anti-PD-L1 blockade d Bhlhe40 programs Trm cell and TIL mitochondrial metabolism and active chromatin state d Epigenetic targeting Trm cell and TIL functional program promotes tumor control

CD8+ tissue-resident memory T (TRM) cells provide frontline immunity in mucosal tissues. The mechanisms regulating CD8+ TRM maintenance, heterogeneity, and protective and pathological functions are largely elusive. Here, we identify a population of CD8+ TRM cells that is maintained by major histocompatibility complex class I (MHC-I) signaling, and CD80 and CD86 costimulation after acute influenza infection. These TRM cells have both exhausted-like phenotypes and memory features and provide heterologous immunity against secondary infection. PD-L1 blockade after the resolution of primary infection promotes the rejuvenation of these exhausted-like TRM cells, restoring protective immunity at the cost of promoting postinfection inflammatory and fibrotic sequelae. Thus, PD-1 serves to limit the pathogenic capacity of exhausted-like TRM cells at the memory phase. Our data indicate that TRM cell exhaustion is the result of a tissue-specific cellular adaptation that balances fibrotic sequelae with protective immunity.

Lower respiratory viral infections, such as influenza virus and severe acute respiratory syndrome coronavirus 2 infections, often cause severe viral pneumonia in aged individuals. Here, we report that influenza viral pneumonia leads to chronic nonresolving lung pathology and exacerbated accumulation of CD8+ tissue-resident memory T cells (TRM) in the respiratory tract of aged hosts. TRM cell accumulation relies on elevated TGF-β present in aged tissues. Further, we show that TRM cells isolated from aged lungs lack a subpopulation characterized by expression of molecules involved in TCR signaling and effector function. Consequently, TRM cells from aged lungs were insufficient to provide heterologous protective immunity. The depletion of CD8+ TRM cells dampens persistent chronic lung inflammation and ameliorates tissue fibrosis in aged, but not young, animals. Collectively, our data demonstrate that age-associated TRM cell malfunction supports chronic lung inflammatory and fibrotic sequelae after viral pneumonia.

Central Asia has a land area of 5.6 × 10(6) km(2) and contains 80-90% of the world's temperate deserts. Yet it is one of the least characterized areas in the estimation of the global carbon (C) stock/balance. This study assessed the sizes and spatiotemporal patterns of C pools in Central Asia using both inventory (based on 353 biomass and 284 soil samples) and process-based modeling approaches. The results showed that the C stock in Central Asia was 31.34-34.16 Pg in the top 1-m soil with another 10.42-11.43 Pg stored in deep soil (1-3 m) of the temperate deserts. They amounted to 18-24% of the global C stock in deserts and dry shrublands. The C stock was comparable to that of the neighboring regions in Eurasia or major drylands around the world (e.g. Australia). However, 90% of Central Asia C pool was stored in soil, and the fraction was much higher than in other regions. Compared to hot deserts of the world, the temperate deserts in Central Asia had relatively high soil organic carbon density. The C stock in Central Asia is under threat from dramatic climate change. During a decadal drought between 1998 and 2008, which was possibly related to protracted La Niña episodes, the dryland lost approximately 0.46 Pg C from 1979 to 2011. The largest C losses were found in northern Kazakhstan, where annual precipitation declined at a rate of 90 mm decade(-1) . The regional C dynamics were mainly determined by changes in the vegetation C pool, and the SOC pool was stable due to the balance between reduced plant-derived C influx and inhibited respiration.

Neutrophils are vital for antimicrobial defense; however, their role during viral infection is less clear. Furthermore, the molecular regulation of neutrophil fate and function at the viral infected sites is largely elusive. Here we report that BCL6 deficiency in myeloid cells exhibited drastically enhanced host resistance to severe influenza A virus (IAV) infection. In contrast to the notion that BCL6 functions to suppress innate inflammation, we find that myeloid BCL6 deficiency diminished lung inflammation without affecting viral loads. Using a series of Cre-transgenic, reporter, and knockout mouse lines, we demonstrate that BCL6 deficiency in neutrophils, but not in monocytes or lung macrophages, attenuated host inflammation and morbidity following IAV infection. Mechanistically, BCL6 bound to the neutrophil gene loci involved in cellular apoptosis in cells specifically at the site of infection. As such, BCL6 disruption resulted in increased expression of apoptotic genes in neutrophils in the respiratory tract, but not in the circulation or bone marrow. Consequently, BCL6 deficiency promoted tissue neutrophil apoptosis. Partial neutrophil depletion led to diminished pulmonary inflammation and decreased host morbidity. Our results reveal a previously unappreciated role of BCL6 in modulating neutrophil apoptosis at the site of infection for the regulation of host disease development following viral infection. Furthermore, our studies indicate that tissue-specific regulation of neutrophil survival modulates host inflammation and tissue immunopathology during acute respiratory viral infection.