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Abstract The roles of Arctic aerosols as ice-nucleating particles remain poorly understood, even though their effects on cloud microphysics are crucial for assessing the climate sensitivity of Arctic mixed-phase clouds and predicting their response to Arctic warming. Here we present a full-year record of ice-nucleating particle concentrations over Svalbard, where surface warming has been anomalously faster than the Arctic average. While the variation of ice-nucleating particles active at around −30 °C was relatively small, those active at higher temperatures (i.e., highly active ice-nucleating particles) tended to increase exponentially with rising surface air temperatures when the surface air temperatures rose above 0 °C and snow/ice-free barren and vegetated areas appeared in Svalbard. The aerosol population relevant to their increase was largely characterized by dust and biological organic materials that likely originated from local/regional terrestrial sources. Our results suggest that highly active ice-nucleating particles could be actively released from Arctic natural sources in response to surface warming.

Abstract Observed trends in tropospheric ozone, an important air pollutant and short‐lived climate forcer (SLCF), are estimated using available surface and ozonesonde profile data for 1993–2019, using a coherent methodology, and compared to modeled trends (1995–2015) from the Arctic Monitoring Assessment Program SLCF 2021 assessment. Increases in observed surface ozone at Arctic coastal sites, notably during winter, and concurrent decreasing trends in surface carbon monoxide, are generally captured by multi‐model median trends. Wintertime increases are also estimated in the free troposphere at most Arctic sites, with decreases during spring months. Winter trends tend to be overestimated by the multi‐model medians. Springtime surface ozone increases in northern coastal Alaska are not simulated while negative springtime trends in northern Scandinavia are not always reproduced. Possible reasons for observed changes and model performance are discussed including decreasing precursor emissions, changing ozone dry deposition, and variability in large‐scale meteorology.

Reduction in key air pollutants, especially particulate carbon, can help mitigate Arctic warming with associated benefits for global climate and human health, according to Earth system model simulations under future emissions scenarios.

Improved air quality is projected to weaken Atlantic Meridional Overturning Circulation but the effects can be offset by methane reductions, according to air quality control simulations based on the Shared Socio-economic Pathways.

Stratospheric meteorite dust particles can be entrained into the upper troposphere by tropopause folding, where the particles may affect cloud formation, according to electron microscopy of extraplanetary materials found within tropospheric sulfate aerosol particles

Abstract Changes in the hydrological cycle in the northern hemisphere (NH) have a significant socioeconomic impact. Thus, quantifying past changes and projecting future changes in this cycle are important. We analyzed the positive and negative multidecadal trends in the NH mean precipitation since the 1950s that were accurately reproduced by a state‐of‐the‐art Earth system model. Results showed that changes in the interhemispheric heat transport play a major role in the NH atmospheric heat budget, accounting for 59% of the negative‐to‐positive trend change in NH precipitation through a north–south shift in the tropical precipitation zone, and were strongly linked to Hadley circulation anomaly. The remaining 41% corresponded to changes in atmospheric cooling with small interhemispheric differences, which were primarily related to clear‐sky longwave radiation. These findings quantitatively agreed with the results from a multimodel analysis.

Abstract The observed sea level (SL) around the Japanese coast shows a peculiar multidecadal variation with the peak in the 1950s followed by the gradual fall until the 1970s and the rebound continuing to the present, making the recent SL rise less remarkable in the historical record. The multidecadal SL variability of an ensemble mean of the Coupled Model Intercomparison Project phase 6 historical simulations using the Meteorological Research Institute Earth System Model version 2.0 (MRI‐ESM2.0) compares well with the observation and is greater than the piControl one, implying the observed variability could be a forced one. The MRI‐ESM2.0 simulations for the Detection and Attribution Model Intercomparison Project suggest the increase in anthropogenic aerosols and greenhouse gases caused the fall and rise of the SL, respectively. Additional sensitivity runs indicate the surface heat loss in the North Pacific due to anthropogenic aerosols plays a dominant role in the SL fall.

Abstract The effective radiative forcing (ERF) of anthropogenic gases and aerosols under present-day conditions relative to preindustrial conditions is estimated using the Meteorological Research Institute Earth System Model version 2.0 (MRI-ESM2.0) as part of the Radiative Forcing Model Intercomparison Project (RFMIP) and Aerosol and Chemistry Model Intercomparison Project (AerChemMIP), endorsed by the sixth phase of the Coupled Model Intercomparison Project (CMIP6). The global mean total anthropogenic net ERF estimate at the top of the atmosphere is 1.96 W m−2 and is composed primarily of positive forcings due to carbon dioxide (1.85 W m−2), methane (0.71 W m−2), and halocarbons (0.30 W m−2) and negative forcing due to the total aerosols (− 1.22 W m−2). The total aerosol ERF consists of 23% from aerosol-radiation interactions (− 0.32 W m−2), 71% from aerosol-cloud interactions (− 0.98 W m−2), and slightly from surface albedo changes caused by aerosols (0.08 W m−2). The ERFs due to aerosol-radiation interactions consist of opposing contributions from light-absorbing black carbon (BC) (0.25 W m−2) and from light-scattering sulfate (− 0.48 W m−2) and organic aerosols (− 0.07 W m−2) and are pronounced over emission source regions. The ERFs due to aerosol-cloud interactions (ERFaci) are prominent over the source and downwind regions, caused by increases in the number concentrations of cloud condensation nuclei and cloud droplets in low-level clouds. Concurrently, increases in the number concentration of ice crystals in high-level clouds (temperatures < –38 °C), primarily induced by anthropogenic BC aerosols, particularly over tropical convective regions, cause both substantial negative shortwave and positive longwave ERFaci values in MRI-ESM2.0. These distinct forcings largely cancel each other; however, significant longwave radiative heating of the atmosphere caused by high-level ice clouds suggests the importance of further studies on the interactions of aerosols with ice clouds. Total anthropogenic net ERFs are almost entirely positive over the Arctic due to contributions from the surface albedo reductions caused by BC. In the Arctic, BC provides the second largest contribution to the positive ERFs after carbon dioxide, suggesting a possible important role of BC in Arctic surface warming.

This work presents an analysis of the effect of climate change on surface ozone discussing the related penalties and benefits around the globe from the global modelling perspective based on simulations with five CMIP6 (Coupled Model Intercomparison Project Phase 6) Earth System Models. As part of AerChemMIP (Aerosol Chemistry Model Intercomparison Project) all models conducted simulation experiments considering future climate (ssp370SST) and present-day climate (ssp370pdSST) under the same future emissions trajectory (SSP3-7.0). A multi-model global average climate change benefit on surface ozone of −0.96 ± 0.07 ppbv °C ^−1 is calculated which is mainly linked to the dominating role of enhanced ozone destruction with higher water vapour abundances under a warmer climate. Over regions remote from pollution sources, there is a robust decline in mean surface ozone concentration on an annual basis as well as for boreal winter and summer varying spatially from −0.2 to −2 ppbv °C ^−1 , with strongest decline over tropical oceanic regions. The implication is that over regions remote from pollution sources (except over the Arctic) there is a consistent climate change benefit for baseline ozone due to global warming. However, ozone increases over regions close to anthropogenic pollution sources or close to enhanced natural biogenic volatile organic compounds emission sources with a rate ranging regionally from 0.2 to 2 ppbv C ^−1 , implying a regional surface ozone penalty due to global warming. Overall, the future climate change enhances the efficiency of precursor emissions to generate surface ozone in polluted regions and thus the magnitude of this effect depends on the regional emission changes considered in this study within the SSP3_7.0 scenario. The comparison of the climate change impact effect on surface ozone versus the combined effect of climate and emission changes indicates the dominant role of precursor emission changes in projecting surface ozone concentrations under future climate change scenarios.

Near-term climate forcers (NTCFs), including aerosols and chemically reactive gases such as tropospheric ozone and methane, offer a potential way to mitigate climate change and improve air quality—so called ‘win-win’ mitigation policies. Prior studies support improved air quality under NTCF mitigation, but with conflicting climate impacts that range from a significant reduction in the rate of global warming to only a modest impact. Here, we use state-of-the-art chemistry-climate model simulations conducted as part of the Aerosol and Chemistry Model Intercomparison Project (AerChemMIP) to quantify the 21st-century impact of NTCF reductions, using a realistic future emission scenario with a consistent air quality policy. Non-methane NTCF (NMNTCF; aerosols and ozone precursors) mitigation improves air quality, but leads to significant increases in global mean precipitation of 1.3% by mid-century and 1.4% by end-of-the-century, and corresponding surface warming of 0.23 and 0.21 K. NTCF (all-NTCF; including methane) mitigation further improves air quality, with larger reductions of up to 45% for ozone pollution, while offsetting half of the wetting by mid-century (0.7% increase) and all the wetting by end-of-the-century (non-significant 0.1% increase) and leading to surface cooling of −0.15 K by mid-century and −0.50 K by end-of-the-century. This suggests that methane mitigation offsets warming induced from reductions in NMNTCFs, while also leading to net improvements in air quality.

We previously found that a maximum innate inflammatory response induced by stimulation of Toll-like receptors (TLRs) 3, 7 and 9 requires ERα, but does not require estrogen in multiple cell types from both control and lupus-prone mice. Given the estrogen-independence, we hypothesized that ERα mediates TLR signaling by tethering to, and enhancing, the activity of downstream transcription factors such as NFκB, rather than acting classically by binding EREs on target genes. To investigate the mechanism of ERα impact on TLR signaling, we utilized mice with a knock-in ERα mutant that is unable to bind ERE. After stimulation with TLR ligands, both ex vivo spleen cells and bone marrow-derived dendritic cells (BM-DCs) isolated from mutant ERα ("KIKO") mice produced significantly less IL-6 compared with cells from wild-type (WT) littermates. These results suggest that ERα modulation of TLR signaling does indeed require ERE binding for its effect on the innate immune response.

Recent advancements in T cell immunotherapy suggest that T cells engineered with high-affinity TCR can offer better tumor regression. However, whether a high-affinity TCR alone is sufficient to control tumor growth, or the T cell subset bearing the TCR is also important remains unclear. Using the human tyrosinase epitope-reactive, CD8-independent, high-affinity TCR isolated from MHC class I-restricted CD4(+) T cells obtained from tumor-infiltrating lymphocytes (TIL) of a metastatic melanoma patient, we developed a novel TCR transgenic mouse with a C57BL/6 background. This HLA-A2-restricted TCR was positively selected on both CD4(+) and CD8(+) single-positive cells. However, when the TCR transgenic mouse was developed with a HLA-A2 background, the transgenic TCR was primarily expressed by CD3(+)CD4(-)CD8(-) double-negative T cells. TIL 1383I TCR transgenic CD4(+), CD8(+), and CD4(-)CD8(-) T cells were functional and retained the ability to control tumor growth without the need for vaccination or cytokine support in vivo. Furthermore, the HLA-A2(+)/human tyrosinase TCR double-transgenic mice developed spontaneous hair depigmentation and had visual defects that progressed with age. Our data show that the expression of the high-affinity TIL 1383I TCR alone in CD3(+) T cells is sufficient to control the growth of murine and human melanoma, and the presence or absence of CD4 and CD8 coreceptors had little effect on its functional capacity.

Adoptive T-cell therapy holds great promise for the treatment of metastatic melanoma. However, prohibitive costs associated with current technology required for culture and expansion of tumor-reactive T-cells, the need for intense preconditioning regimens to induce lymphopenia, and the unpredictable anti-tumor effect of adoptively transferred T-cells remain significant impediments for its clinical implementation. Here we report a simplified combinatorial approach that involves short activation of CD8(+) T cells in the presence of IL-12 followed by adoptive transfer into tumor bearing animals after a single injection of cyclophosphamide. This approach resulted in complete eradication of B16 melanoma, and the establishment of long term immunological memory capable of fully protecting mice after a second B16 melanoma challenge. The activated donor cells were unique because they simultaneously exhibited traits for cytotoxic effector function, central memory-like, homing, and senescence. After tumor eradication and within three months after transfer, CD8+ cells exhibited a conventional memory CTL phenotype. Moreover, these memory CTLs acquired functional attributes characteristic of memory stem cells, including the ability to resist chemotherapy-induced toxicity. Our results suggest that short-term T-cell receptor signaling in the presence of IL-12 promotes promiscuous qualities in naïve CTL which - upon transfer into lymphopenic hosts- are sufficient to eradicate tumors and generate life-long tumor-specific memory.

Recent preclinical studies suggest that vaccination following adoptive transfer of CD8(+) T cells into a lymphopenic host can augment the therapeutic antitumor responses of the transferred cells. However, the mechanism by which the lymphopenic microenvironment benefits Ag-specific CD8(+) T cell responses remains elusive. We show herein that induction of lymphodepletion by a single 4 mg cyclophosphamide (CTX) treatment induces a marked expansion of immature dendritic cells (DCs) in the peripheral blood on days 8-16 post-CTX (termed restoration phase). In vitro, these DCs were functional, because they showed normal phagocytosis and effective Ag presentation capability upon activation. In vivo, administration of the TLR3 agonist poly(I:C) at the peak of DC expansion (day 12 postlymphopenia) induced inflammatory cytokine production and increases in the number of activated DCs in lymph nodes. Importantly, boosting with gp100(25-33) melanoma peptide combined with poly(I:C) 12 days after an initial priming with the same regimen significantly increased the expansion and the antitumor efficacy of adoptively transferred pmel-1 CD8(+) T cells. These responses were abrogated after depletion of activated DCs during Ag boosting. In conclusion, our data show that CTX treatment induces, during the restoration phase, expansion of immature DCs, which are functional and can be exploited in vivo to foster more effective antitumor adoptive immunotherapy strategies.