Regulatory T cells (Tregs) expressing the Foxp3 transcription factor are indispensable for the maintenance of immune system homeostasis. Tregs may lose Foxp3 expression or be reprogrammed into cells that produce proinflammatory cytokines, for example, Th1-like Tregs, Th2-like Tregs, Th17-like Tregs, and Tfh-like Tregs. Accordingly, selective therapeutic molecules that manipulate Treg lineage stability and/or functional activity might have the potential to improve aberrant immune responses in human disorders. In particular, the transcription factor Helios has emerged as an important marker and modulator of Tregs. Therefore, the current review focuses on recent findings on the expression, function, and mechanisms of Helios, as well as the patterns of Foxp3⁺ Tregs coexpressing Helios in various human disorders, in order to explore the potential of Helios for the improvement of many immune-related diseases. The studies were selected from PubMed using the library of the Nanjing Medical University in this review. The findings of the included studies indicate that Helios expression stabilizes the phenotype and function of Foxp3⁺ Tregs in certain inflammatory environments. Further, Tregs coexpressing Helios and Foxp3 were identified as a specific phenotype of stronger suppressor immune cells in both humans and animal models. Importantly, there is ample evidence that Helios-expressing Foxp3⁺ Tregs are relevant to various human disorders, including connective tissue diseases, infectious diseases, solid organ transplantation-related immunity, and cancer. Thus, Helios⁺Foxp3⁺CD4⁺ Tregs could be a valuable target in human diseases, and their potential should be explored further in the clinical setting.

Background: RORγt⁺Foxp3⁺ (Th17-like) Tregs are a plastic Treg subset implicated in immune-related diseases; however, the mechanism of Treg phenotypic transformation in malignant pleural effusion (MPE) has not been elucidated. Methods: The percentage of CD4⁺CD25⁺Foxp3⁺Helios⁺ and RORγt⁺Foxp3⁺ Tregs from peripheral blood and pleural effusion mononuclear cells were measured. The level of interferon regulatory factor 4 (IRF4) mRNA expression was detected by quantitative real-time reverse transcription polymerase chain reaction. The effects of IRF4 on the induction of Tregs from patients with non-small cell lung cancer (NSCLC) were evaluated in vitro. Correlation assays between IRF4 expression and the frequency of RORγt⁺Foxp3⁺ Tregs were performed. Results: The frequency of CD4⁺CD25⁺Foxp3⁺Helios⁺ Tregs and CD4⁺RORγt⁺ Th17 cells was both increased in the MPE of NSCLC patients. The group of double-positive Foxp3⁺RORγt⁺ Treg phenotype were identified in the pleural effusion. A significant increase in the frequency of Foxp3⁺RORγt⁺ Tregs was found in MPE compared with the non-malignant pleural effusion (NPE). Compared to NPE, the relative level of IRF4 expression was increased in the MPE. IRF4 expression was positively associated with the frequency of Foxp3⁺RORγt⁺ Tregs in the PE. In vitro, the level of Helios mRNA and protein expression was reduced in induced Tregs following IRF4 over-expression. Additionally, the level of RORγt protein expression was substantially increased. However, ectopic Helios expression in induced Tregs reversed the effects induced by enhanced IRF4 expression. Conclusion: IRF4 may serve as a potential molecule that promotes the conversion of regulatory T cells from MPE to a Th17-like phenotype by modulating Helios.

This report describes a 59-year-old woman with a history of malignancy and post-tuberculosis lung disease complicated by chronic cavitary pulmonary aspergillosis. She was admitted with worsening hemoptysis and underwent bronchial artery embolization. However, she subsequently developed massive post-procedural hemoptysis, requiring mechanical ventilation. Sputum metagenomic next-generation sequencing detected SARS-CoV-2 and bacterial pathogens, prompting Paxlovid treatment for COVID-19 pneumonia. While her respiratory symptoms improved, epigastric pain developed. Based on elevated serum amylase/lipase and CT-confirmed peripancreatic inflammation, she was diagnosed with acute pancreatitis. One year later, pulmonary tuberculosis and liver metastasis recurred. This case highlights acute pancreatitis temporally associated with COVID-19 pneumonia in a patient with multiple competing risk factors. Further, this case underscores the diagnostic complexity of structural lung disease with overlapping infections such as COVID-19 and stresses on the need for long-term surveillance.

Over 200 different serogroups of Vibrio cholerae based on O-polysaccharide specificity have been described worldwide, including the two most important serogroups, O1 and O139. Non-O1/non-O139 V. cholerae serogroups generally do not produce the cholera-causing toxin but do sporadically cause gastroenteritis and extra-intestinal infections. Recently, however, bloodstream infections caused by non-O1/non-O139 V. cholerae are being increasingly reported, and these infections are associated with high mortality in immunocompromised hosts. We describe a case of non-O1/non-O139 V. cholerae bacteremia in a patient with autoimmune pancreatitis and stenosis of the intra- and extrahepatic bile ducts. The clinical manifestations of bacteremia were fever and mild digestive symptoms. The blood cultures showed V. cholerae, which was identified as a non-O1, non-O139 serogroup by slide agglutination tests and PCR. The bloodstream infection of the patient was likely caused by the consumption of contaminated seafood at a banquet. The patient recovered after the administration of a third-generation cephalosporin. Non-O1/non-O139 V. cholerae infection presents with or without gastrointestinal manifestations; close attention should be paid to the possibility of disseminated non-O1/non-O139 V. cholerae infection in high-risk patients.

Secreted and Transmembrane Protein 1 (SECTM1) is a versatile immunomodulatory protein that exists in both membrane-bound and soluble forms. Initially identified for its interaction with the T-cell receptor CD7, it was primarily regarded as a co-stimulatory molecule restricted to lymphoid signaling. Recent evidence has significantly expanded this paradigm, revealing that SECTM1 serves as a pivotal bridge between innate and adaptive immune responses. Beyond its classic role, SECTM1 interacts with alternative receptors like the glucocorticoid-induced TNFR-related protein to regulate macrophage activity and neutrophilic inflammation. This review highlights a major shift in our understanding of SECTM1: it acts as a multi-systemic regulator that influences the tumor microenvironment, metabolic homeostasis, and tissue regeneration. We systematically delineate the molecular mechanisms by which SECTM1 governs immune cell migration and activation across diverse pathologies, including cancer, cardiovascular disorders, and neurodegenerative diseases. By positioning SECTM1 as a marker of “immune-hot” tumors and a potential early diagnostic biomarker for systemic conditions, this work underscores its emerging clinical potential as a target for precision immunotherapy and regenerative medicine.