Safety/efficacy of atezolizumab + bevacizumab during anti-platelet/anticoagulation therapy in unresectable hepatocellular carcinoma.

BACKGROUND AND AIMS: This study aimed to determine the safety and efficacy of atezolizumab + bevacizumab therapy in hepatocellular carcinoma patients receiving anti-platelet agents or anticoagulants. METHODS: Patients were divided into those using (IM out) and those not using (IM in) anti-platelet agents or anticoagulants, who violated the exclusion criteria of the IMbrave150 trial, and were retrospectively examined. RESULTS: The study included 185 patients (IM in: 157; IM out: 28). For first-line treatment, progression-free survival was 184 days for IM in and 266 days for IM out (p = .136). Overall survival was 603 days for IM in and not reached for IM out (p = .265), with no significant between-group difference. Similarly, there were no significant between-group differences in progression-free survival or overall survival for later-line treatment. Haemorrhagic adverse events of ≥grade 3 were observed in 11 IM in patients and 3 IM out patients. No significant factors associated with haemorrhagic adverse events of ≥grade 3 were identified in the multivariate analysis including IM out classification, whose p value was .547. Regarding thrombotic/embolic adverse events in the IM out group, one case of exacerbation of portal vein thrombosis was observed. No deaths were directly attributable to bleeding events or exacerbations of thrombosis. CONCLUSION: Atezolizumab + bevacizumab therapy shows similar safety and efficacy in patients receiving and those not receiving anti-platelet agents or anticoagulants; therefore, it can be considered for patients with hepatocellular carcinoma receiving anti-platelet agents or anticoagulants.

Pembrolizumab-induced asthma exacerbation with hypereosinophilia and elevated interleukin-5 in endometrial cancer: A case report.

Pembrolizumab is an anti-programmed cell death-1 (PD-1) antibody used to treat various cancer types. Treatments with such immune checkpoint inhibitors cause immune-related adverse events. However, airway inflammation caused by immune-related adverse events has rarely been reported. A 54-year-old woman with endometrial cancer experienced asthma exacerbation, and increased blood eosinophil counts 3 months after pembrolizumab administration. Although asthma exacerbation improved, the resumption of pembrolizumab caused the recurrence of dry cough and hypereosinophilia. The discontinuation of pembrolizumab improved her symptoms. Serum interleukin-5 levels increased during pembrolizumab treatment but decreased upon discontinuation. The blockade of PD-1 and its ligand may exacerbate asthma through eosinophilic inflammation.

Efficacy, Safety, and Continuation of Biological Therapy in Older Patients with Asthma in a Real-World Setting: A Retrospective Observational Study.

Background: Major randomized clinical trials have shown that biological therapy can reduce the exacerbation rate and oral corticosteroid (OCS) dosage in patients with severe eosinophilic asthma. However, data on the continuation, efficacy, and safety of biological therapy in older patients with asthma are limited. Therefore, the aim of this study was to evaluate the differences in the continuation rate, efficacy, and safety of biological therapy between older (≥ 65 years) and younger (< 65 years) patients with asthma. Methods: In this single-center retrospective observational study, we collected clinical data of patients with asthma who were administered biological drugs such as omalizumab, mepolizumab, benralizumab, and dupilumab between April 2009 and August 2022. We comparatively analyzed the continuation, efficacy, and safety of biological therapy between older (age ≥ 65 years) and younger patient (age < 65 years) groups. The reasons for discontinuation or switching of biological drugs were also evaluated. Results: Sixty-two (31 older and 31 younger) patients were treated with 91 biologics during the observational period. The mean age of older patients was 74.3 ± 5.1 years and that of younger patients was 48.0 ± 14.0 years. The continuation rate of biological therapy was not significantly different between the groups. Social background was the most common reason for discontinuation of biological therapy in both groups, and insufficient effect was the most common reason for switching to biological drugs. Asthma exacerbations decreased in both groups within the first 12 months of biologic therapy. The dosage of OCS tended to decrease in the older group and significantly decrease in the younger group. Conclusion: Biologic therapy for older patients with asthma can be continued, with efficacy and safety similar to those in younger patients with asthma.

Group2 innate lymphoid cells ameliorate renal fibrosis and dysfunction associated with adenine-induced CKD.

Renal fibrosis is a common pathway of chronic kidney disease (CKD) progression involving primary kidney injury and kidney diseases. Group 2 innate lymphoid cells (ILC2s) mediate type 2 immune responses irrespective of antigen presentation and play a reno-protective role in kidney injury and disease. In the present study, we observed a decrease in kidney-resident ILC2s in CKD and found that enrichment of ILC2s in the kidney ameliorates renal fibrosis. In CKD kidney, ILC2s preferentially produced IL-13 over IL-5 in response to IL-33 stimulation, regardless of ST2L expression. Moreover, GATA3 expression was decreased in ILC2s, and T-bet+ ILC1s and RORγt+ ILC3s were increased in CKD kidney. Adoptive transfer of kidney ILC2s into adenine-induced CKD model mouse improved renal function and fibrosis. Renal fibroblasts cultured with IL33-activated kidney ILC2s suppressed myofibroblast trans-differentiation through Acta2 and Fn-1 regulation. These results suggest that kidney ILC2s prevent CKD progression via improvement of renal fibrosis. Our findings also suggest that ILC2s may contribute to the development of new therapeutic agents and strategies for tissue fibroses.

Medial Meniscus Posterior Root Reconstruction and Open-Wedge High-Tibial Osteotomy for Medial Meniscus Posterior Root Tear With Varus Knee Alignment: A Retrospective Study on Short-Term Outcomes.

PURPOSE: We describe 13 cases of medial meniscus posterior root tear (MMPRT) with varus knee alignment treated with medial meniscus posterior root reconstruction (MMPR-R) and open-wedge high-tibial osteotomy (OWHTO) to identify an optimal MMPRT treatment. METHODS: We retrospectively reviewed 13 patients (mean age: 66.3 ± 8.0 years) who underwent MMPR-R and OWHTO. The Knee Injury and Osteoarthritis Outcome Score (KOOS), femorotibial angle (FTA), percentage mechanical axis (%MA) on radiography, and medial meniscus extrusion (MME) on magnetic resonance imaging (MRI) between the preoperative period and last follow-up were compared. Moreover, meniscus healing status and the International Cartilage Repair Society (ICRS) classification of the medial femoral condyle and medial tibial plateau on arthroscopy between the initial surgery and second-look arthroscopy were compared. RESULTS: The mean follow-up duration was 12.8 ± 2.2 months. At the last follow-up, the KOOS significantly improved (P < 0.01). Based on the FTA and %MA, the varus alignment was predominantly corrected at the last follow-up (P < 0.01). The MME was increased in nine (62.9%) patients, and the mean MME significantly increased at the last follow-up (P = 0.04). Second-look arthroscopy revealed improvements in the ICRS grade for the medial femoral condyle and medial tibial plateau in six (46.2%) patients. However, the results did not significantly differ. Regarding meniscus healing, four (30.8%) patients presented with complete healing, eight (57.1%) with partial healing, and one (7.7%) with failed healing. CONCLUSIONS: The MMPRT with varus knee alignment significantly improved with MMPR-R and OWHTO. However, the MME and meniscus healing were unsatisfactory.

In vitro investigation of the effects of Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 exopolysaccharides on tight junction damage caused by influenza virus infection.

It is a problem that influenza virus infection increases susceptibility to secondary bacterial infection in lungs leading to lethal pneumonia. We previously reported that exopolysaccharides (EPS) derived from Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 (OLL1073R-1) could prevent against influenza virus infection followed by secondary bacterial infection in vitro. Therefore, the present study assessed whether EPS derived OLL1073R-1 protects the alveolar epithelial barrier disfunction caused by influenza virus infection. After A549 cells treated with EPS or without EPS were infected influenza virus A/Puerto Rico/8/34 (IFV) for 12 h, the levels of tight junction genes expression and inflammatory genes expression were measured by reverse transcription polymerase chain reaction. As results, EPS treatment could protect against low-titer IFV infection, but not high-titer IFV infection, followed by suppression of the increased expression of inflammatory cytokine gene levels and recovery of the decrease in the expression level of ZO-1 gene that was caused by low-titer IFV infection, leading to an improvement trend in the barrier function. Our findings showed that EPS derived from OLL1073R-1 could inhibit low-titer IFV infection leading to maintenance of the epithelial barrier function through the suppression of inflammatory cytokine genes expression.

Transmission electron microscopic study of the surface layer of surgical resected disc specimens in human temporomandibular joint.

In this study, we investigated specific and characteristic findings of the surface layer of surgical resected disc specimens in human temporomandibular joint osteoarthritis cases by transmission electron microscopy (TEM).Specimens were surgically removed from the TMJ of 5 cases (4 female patients: 5 cases) clinically osteoarthritis. Following findings were observed by TEM. Images were photographed on a JEM1400-Flash Electron microscope (JEOL, Japan) equipped with an EM-14661FLASH high-sensitivity digital complementary metal-oxide-semiconductor camera.Following findings were observed by TEM. 1) The surface is covered with plump fibroblastic and histiocytoid cells. 2) Collagen fiber bundles and collagenous matrix are exposed onto the eroded disc surface. 3) Fibrinous dense material is observed on the eroded disc surface. 4) Bundles of collagen fibers are densely observed. 5) Collagen bundles are rich around capillary vessels. 6) Synovial surface cells reveal features of activated macrophages with vacuole formation. Especially, plump fibroblastic and histiocytoid cells, and activated macrophages with vacuole, which were significant findings of the surface layer. These findings might have a significant effect on the regulation of synovial fluid.

Osteosynthesis with Arthroscopy of a Nonunited Tibial Anterior Cruciate Ligament Avulsion Fracture 30 Years after Injury.

There are a few reports on the treatment of nonunited tibial anterior cruciate ligament (ACL) avulsion fractures. To our knowledge, this is the first report of a case of nonunited tibial ACL avulsion fracture 30 years after injury. A 36-year-old woman injured her knee during a road traffic accident 30 years ago. Since then, she had persistent knee instability that was left untreated. She presented to our clinic because of knee pain she had been experiencing for a week. Radiography and computed tomography revealed tibial ACL avulsion fracture nonunions. Screw fixation with arthroscopy was performed, and bone fusion was obtained. The knee injury and osteoarthritis outcome score improved from 24 points preoperatively to 83 points postoperatively. The nonunion of intercondylar eminence fractures of the tibia, even up to 30 years after the initial injury, can be treated by osteosynthesis with arthroscopy.

Effects of NKT Cells on Metabolic Disorders Caused by High-Fat Diet Using CD1d-Knockout Mice.

Purpose: The purpose of this study was to investigate whether NKT cells play an important role in preventing or exacerbating diseases caused by high-fat diet (HFD) using CD1d-knockout (KO) mice which lack NKT cells. Methods: Five-week-old male Balb/c (wild-type; WT) or CD1dKO mice were fed with control-diet (CTD) or HFD for 16 weeks. Results: The present study revealed four main findings. First, CD1dKO mice were susceptible to obesity caused by HFD in comparison to WT mice. Second, clinical conditions of fatty liver caused by HFD were comparable between CD1dKO mice and WT mice. Third, HFD-fed WT mice showed high levels of serum biochemical markers, involved in lipid metabolisms, in comparison to WT mice fed a CTD. Notably, the serum concentrations of ALT, T-CHO, TG and HDL-C in CD1dKO mice fed a HFD were almost comparable to those of CD1dKO mice fed a CTD. Fourth, the expression of peroxisome proliferator-activated receptor (PPAR) γ, low-density lipoprotein receptor (LDLR), CD36 of epididymal adipose tissue enhanced and proprotein convertase subtilisin/kexin type (PCSK) 9 in serum decreased. Conclusion: NKT cells were responsible for protection against HFD-induced obesity. However, CD1dKO mice were resistant to serum biochemical marker abnormalities after HFD feeding. One possible explanation is that the epididymal adipose tissue of CD1dKO mice could take up greater amounts of excess lipids in serum in comparison to WT mice.

The essential role of intestinal microbiota in cytomegalovirus reactivation.

Human cytomegalovirus (HCMV) is a member of Herpesviridae. It has been reported that HCMV is reactivated in the breast milk of HCMV-seropositive lactating women. As we have reported various aspects of the roles of indigenous microbiota, its role in the murine CMV (MCMV) reactivation was examined in this study. MCMV was latently infected in the salivary gland, mammary tissues, and colon in the pregnant mice. When the salivary gland, mammary tissues, and colon were removed 5 days after delivery, MCMV reactivation of latent infection in each organ was confirmed by the detection of MCMV IE1 mRNA using reverse transcription-quantitative PCR. MCMV reactivation was observed in 100% of the mice during pregnancy. Next, for the elimination of intestinal microbiota, the pregnant mice were treated with low-dose or high-dose non-absorbable antibiotics. Although the numbers of aerobe/anaerobe in cecal content in low-dose antibiotic-treated mice were comparable to those in untreated controls, high-dose antibiotic treatment decreased the number of aerobe/anaerobe microbes from ca.9.0 Log10 to ca.3.0 Log10 (cfu/g). However, it could not be confirmed in 16S rRNA analysis that specific bacterial phylum or genus was eliminated by this high-dose treatment. Interestingly, MCMV reactivation was also observed in 100% of low-dose antibiotic-treated mice, whereas, in high-dose antibiotic-treated mice, MCMV reactivation was not observed in the salivary gland or colon. MCMV IE1 mRNA was detected only in 33% of the mammary tissues of those high-dose-treated mice. These results suggest that the indigenous microbiota played a crucial role in the reactivation of latent infection. IMPORTANCE Human cytomegalovirus (HCMV) infection via breast milk is a serious problem for very preterm infants such as developing a sepsis-like syndrome, cholestasis, or bronchopulmonary dysplasia, among others. It has been reported that HCMV is reactivated in the breast milk of HCMV-seropositive lactating women. In this study, the roles of indigenous microbiota in the murine CMV (MCMV) reactivation were examined using a mouse model. In MCMV latently infected mice, MCMV reactivation was observed in 100% of the mice during pregnancy. For the elimination of intestinal microbiota, MCMV-latent mice were treated with non-absorbable antibiotics. After delivery, MCMV reactivation was not observed in antibiotic-treated mice. This result suggested that the indigenous microbiota played a crucial role in the reactivation of latent infection.

Type V Tibial Tubercle Avulsion Fracture with Suspected Complication of Anterior Cruciate Ligament Injury: A Case Report.

Background and Objectives: Type V tibial tubercle avulsion fractures are extremely rare; therefore, information on them remains limited. Furthermore, although these fractures are intra-articular, to the best of our knowledge, there are no reports on their assessment via magnetic resonance imaging (MRI) or arthroscopy. Accordingly, this is the first report to describe the case of a patient undergoing detailed evaluation via MRI and arthroscopy. Case Presentation: A 13-year-old male adolescent athlete jumped while playing basketball, experienced discomfort and pain at the front of his knee, and fell down. He was transported to the emergency room by ambulance after he was unable to walk. The radiographic examination revealed a Type Ⅴ tibial tubercle avulsion fracture that was displaced. In addition, an MRI scan revealed a fracture line extending to the attachment of the anterior cruciate ligament (ACL); moreover, high MRI intensity and swelling due to ACL were observed, suggesting an ACL injury. On day 4 of the injury, open reduction and internal fixation were performed. Furthermore, 4 months after surgery, bone fusion was confirmed, and metal removal was performed. Simultaneously, an MRI scan obtained at the time of injury revealed findings suggestive of ACL injury; therefore, an arthroscopy was performed. Notably, no parenchymal ACL injury was observed, and the meniscus was intact. The patient returned to sports 6 months postoperatively. Conclusion: Type V tibial tubercle avulsion fractures are known to be extremely rare. Based on our report, we suggest that MRI should be performed without hesitation if intra-articular injury is suspected.

The Clinical Characteristics of Allergic Bronchopulmonary Mycosis Differ Among Pathogenic Fungi.

Background: Allergic bronchopulmonary mycosis (ABPM) occurs with fungi, other than Aspergillus fumigatus. However, the clinical characteristics of ABPM caused by non-Aspergillus species are unspecified. Methods: We retrospectively reviewed all patients with ABPM who visited to our hospital between April 2005 and December 2020. The causative fungi and clinical characteristics were analyzed. Patients were divided into the Aspergillus group and the non-Aspergillus group. Results: Fourteen patients and five patients were included in the Aspergillus group and the non-Aspergillus group, respectively. Compared to the Aspergillus group, the non-Aspergillus group had a significantly low serum immunoglobulin E level and low forced vital capacity. In addition, the non-Aspergillus group had a lower rate of the requirement for oral corticosteroid treatment and a low frequency of recurrence. Conclusion: Patients with non-Aspergillus ABPM had lower type 2 inflammation than did patients with allergic bronchopulmonary aspergillosis.

Human immune and gut microbial parameters associated with inter-individual variations in COVID-19 mRNA vaccine-induced immunity.

COVID-19 mRNA vaccines induce protective adaptive immunity against SARS-CoV-2 in most individuals, but there is wide variation in levels of vaccine-induced antibody and T-cell responses. However, the mechanisms underlying this inter-individual variation remain unclear. Here, using a systems biology approach based on multi-omics analyses of human blood and stool samples, we identified several factors that are associated with COVID-19 vaccine-induced adaptive immune responses. BNT162b2-induced T cell response is positively associated with late monocyte responses and inversely associated with baseline mRNA expression of activation protein 1 (AP-1) transcription factors. Interestingly, the gut microbial fucose/rhamnose degradation pathway is positively correlated with mRNA expression of AP-1, as well as a gene encoding an enzyme producing prostaglandin E2 (PGE2), which promotes AP-1 expression, and inversely correlated with BNT162b2-induced T-cell responses. These results suggest that baseline AP-1 expression, which is affected by commensal microbial activity, is a negative correlate of BNT162b2-induced T-cell responses.

Effect of Ethanol Vapor Inhalation Treatment on Lethal Respiratory Viral Infection With Influenza A.

Ethanol (EtOH) effectively inactivates enveloped viruses in vitro, including influenza and severe acute respiratory syndrome coronavirus 2. Inhaled EtOH vapor may inhibit viral infection in mammalian respiratory tracts, but this has not yet been demonstrated. Here we report that unexpectedly low EtOH concentrations in solution, approximately 20% (vol/vol), rapidly inactivate influenza A virus (IAV) at mammalian body temperature and are not toxic to lung epithelial cells on apical exposure. Furthermore, brief exposure to 20% (vol/vol) EtOH decreases progeny virus production in IAV-infected cells. Using an EtOH vapor exposure system that is expected to expose murine respiratory tracts to 20% (vol/vol) EtOH solution by gas-liquid equilibrium, we demonstrate that brief EtOH vapor inhalation twice a day protects mice from lethal IAV respiratory infection by reducing viruses in the lungs without harmful side effects. Our data suggest that EtOH vapor inhalation may provide a versatile therapy against various respiratory viral infectious diseases.

Phosphoenolpyruvate regulates the Th17 transcriptional program and inhibits autoimmunity.

Aerobic glycolysis, a metabolic pathway essential for effector T cell survival and proliferation, regulates differentiation of autoimmune T helper (Th) 17 cells, but the mechanism underlying this regulation is largely unknown. Here, we identify a glycolytic intermediate metabolite, phosphoenolpyruvate (PEP), as a negative regulator of Th17 differentiation. PEP supplementation or inhibition of downstream glycolytic enzymes in differentiating Th17 cells increases intracellular PEP levels and inhibits interleukin (IL)-17A expression. PEP supplementation inhibits expression of signature molecules for Th17 and Th2 cells but does not significantly affect glycolysis, cell proliferation, or survival of T helper cells. Mechanistically, PEP binds to JunB and inhibits DNA binding of the JunB/basic leucine zipper transcription factor ATF-like (BATF)/interferon regulatory factor 4 (IRF4) complex, thereby modulating the Th17 transcriptional program. Furthermore, daily administration of PEP to mice inhibits generation of Th17 cells and ameliorates Th17-dependent autoimmune encephalomyelitis. These data demonstrate that PEP links aerobic glycolysis to the Th17 transcriptional program, suggesting the therapeutic potential of PEP for autoimmune diseases.

Asymmetric Hydrogenation of α-Amino Esters into Optically Active ß-Amino Alcohols through Dynamic Kinetic Resolution Catalyzed by Ruthenabicyclic Complexes.

Racemic α-substituted α-amino esters were hydrogenated into enantioenriched ß-amino alcohols through dynamic kinetic resolution with chiral ruthenabicyclic complexes. The reaction was carried out with a substrate/catalyst molar ratio of 200-1000 under 15 atm of H2 at 25 °C to afford a variety of ß-substituted ß-aminoethanols in up to 96% ee (24 examples). The mechanistic studies including deuteration experiments suggested that the reaction proceeds with 1,2-hydride migration of the α-amino acetalate intermediate into the α-hydroxy imine followed by the continuous reduction of the imino compound, affording the amino alcohol product.

HIF-PHD inhibitor regulates the function of group2 innate lymphoid cells and polarization of M2 macrophages.

Hypoxia-inducible factor-prolyl hydroxylase (HIF-PHD) inhibitors are therapeutic agents for renal anemia that work through HIF2-mediated upregulation of erythropoietin (EPO) and have also been reported to suppress renal fibrosis. Group 2 innate lymphoid cells (ILC2s) have been proven to be involved in the pathogenesis of fibrosis in various organs, including the kidney. However, the relationship between the HIF pathway, renal fibrosis, and kidney ILC2s remains unclear. In the present study, we found that HIF activation by HIF-PHD inhibitors suppressed type 2 cytokine production from kidney ILC2s. The enhanced HIF pathway downregulated the IL-33 receptor ST2L on ILC2s, and phosphorylation of downstream p38 MAPK was attenuated. M2 macrophages that promote renal fibrosis were polarized by ILC2 supernatants, but reduced cytokine production from ILC2s treated with HIF-PHD inhibitors suppressed this polarization. Our findings suggest that HIF-PHD inhibitors are potential therapeutic agents for renal fibrosis that are mediated by the alteration of ILC2 function.

Reactions to a dead adult female in Japanese macaques at Arashiyama: Why did a non-affiliated female groom the corpse?

Reporting reactions to death in nonhuman primates can provide valuable information for understanding the evolutionary origin of human ways of dealing with death. Although many studies have reported nonhuman primates' reactions to infant corpses, less is known about their reactions toward dead adults or adolescents. The deaths of adult primates, who usually form complex social relationships, may have social impacts. Here, we described in detail the reactions of Japanese macaques (Macaca fuscata) to the corpse of an adult female in a free-ranging multi-male multi-female group. We analyzed quantitative data on the whole group to determine how death-related behaviors were related to social relationships. Most group members in this case, including social partners of the deceased, exhibited no notable interest in the corpse. Only one adult female, who was not a grooming partner of the female before she died, touched and groomed the corpse. We examined four possible reasons why this female groomed the corpse: unawareness of death, learning about death, desire to consume insects, and reputation-building with other group members. This study highlights the potential value of closer examination of associations between reactions to dead adults or adolescents and social relationships before and after death in primate groups.

Arthroscopic Osteophyte Resection for Osteophyte-Induced Popliteal Impingement.

Popliteal tendinitis causes lateral knee pain. A cause is impingement of the popliteal tendon by lateral femoral condylar osteophytes. Conservative and surgical treatments have been reported; however, popliteal impingement is a relatively rare disease, and no treatment has been established. Reduction of mechanical stress is important in the treatment of impingement syndromes. The popliteal tendon is an important tissue that contributes to knee stability and, therefore, usually cannot be transected. On the other hand, osteophyte resection may allow the reduction of mechanical stress. Therefore, we describe an arthroscopic osteophyte resection technique for the treatment of osteophyte-induced popliteal impingement. In brief, this technique involves confirmation of popliteal impingement, osteophyte resection using an osteotome, smoothening of the resected area, and confirmation of the resolution of popliteal impingement.

JunB Is Critical for Survival of T Helper Cells.

Clonal expansion and differentiation of various T helper subsets, such as Th1, Th2, and Th17 cells, depend on a complex of transcription factors, IRF4 and a BATF-containing AP-1 heterodimer. A major BATF heterodimeric partner, JunB, regulates Th17 differentiation, but the role of JunB in other T helper subsets is not well understood. Here we demonstrate that JunB is required for clonal expansion of Th1, Th2 and Th17 cells. In mice immunized with lipopolysaccharide (LPS), papain, or complete Freund's adjuvant (CFA), which induce predominantly Th1, Th2 and Th17 cells, respectively, accumulation of antigen-primed, Junb-deficient CD4+ T cells is significantly impaired. TCR-stimulated Junb-deficient CD4+ T cells are more sensitive to apoptosis, although they showed largely normal proliferation and cellular metabolism. JunB directly inhibits expression of genes involved in apoptosis, including Bcl2l11 (encoding Bim), by promoting IRF4 DNA binding at the gene locus. Taken together, JunB serves a critical function in clonal expansion of diverse T helper cells by inhibiting their apoptosis.