Type 3 innate lymphoid cells (ILC3s) are key regulators of intestinal homeostasis and epithelial barrier integrity. In this issue of the JCI, Cao and colleagues found that a sensor of endoplasmic reticulum (ER) stress, the inositol-requiring kinase 1α/X-box-binding protein 1 (IRE1α/XBP1) pathway, fine-tuned the functions of ILC3s. Activation of IRE1α and XBP1 in ILC3s limited intestinal inflammation in mice and correlated with the efficacy of ustekinumab, an IL-12/IL-23 blocker, in patients with Crohn\'s disease. These results advance our understanding in the use of ILCs as biomarkers not only to predict disease outcomes but also to indicate the response to biologicals in patients with inflammatory bowel disease.

The aim of the study was to investigate the peculiarities of morphometric parameters of peripheral blood lymphocytes in chronic pyelonephritis in elderly patients in comparison with young and middle-aged patients. A total of 81 patients with chronic pyelonephritis in the exacerbation phase were examined. All patients were divided into three age groups according to WHO recommendations: the 1st - 42patients of young age (18-44 years); the 2nd - 17 patients of middle age (45-59 years); the 3rd - 22 elderly patients (60-74 years). Computer morphometry of lymphocytes was performed in all examined patients. In elderly patients with chronic pyelonephritis the size and сytoplasmic-nuclear ratio of lymphocytes increase. This indicates the preservation of lymphocyte defense responses at this age. In male patients with chronic pyelonephritis in the 1st and 2nd age groups the size of lymphocytes increases, and in female patients - decreases. The сytoplasmic-nuclear ratio increases in males of these age groups, while it remains unchanged or decreases in females. Indirect indications of reduced immunity in young and middle-aged women with chronic inflammation in the kidneys have been obtained.
Цель исследования — изучение особенностей морфометрических параметров лимфоцитов периферической крови при хроническом пиелонефрите у больных пожилого возраста в сравнении с больными молодого и среднего возраста. Обследован 81 больной хроническим пиелонефритом в фазе обострения. Все больные были разделены на три возрастные группы согласно рекомендациям ВОЗ: 1-я — 42 пациента молодого возраста (18–44 года); 2-я — 17 пациентов среднего возраста (45–59 лет); 3-я — 22 пациента пожилого возраста (60–74 года). Всем обследованным проведена компьютерная морфометрия лимфоцитов. У пожилых больных хроническим пиелонефритом размеры и цитоплазменно-ядерное отношение лимфоцитов увеличиваются. Это указывает на сохранность защитных реакций лимфоцитов в этом возрасте. У мужчин, больных хроническим пиелонефритом, в 1-й и 2-й возрастных группах размеры лимфоцитов увеличиваются, а у женщин — уменьшаются. Цитоплазменно-ядерное отношение увеличивается у мужчин этих возрастных групп, у женщин — не меняется или уменьшается. Получены косвенные указания на снижение иммунитета у женщин в молодом и среднем возрасте при развитии хронического воспаления в почках.

BACKGROUND: Neutrophil to lymphocyte ratio (NLR) has been considered a prognostic biomarker of mortality and other major cardiac events. This study investigates NLR\'s efficacy in predicting in-hospital and long-term outcomes in patients with ST-segment elevated myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI).
METHODS: Electronic databases (PUBMED, Cochrane CENTRAL, ERIC, Embase, Ovid, and Google Scholar) were searched till June 2022 to identify studies having STEMI patients who underwent PCI. Risk ratios and mean differences (MDs), along with their corresponding 95% confidence intervals (Cis) and standard deviations (SDs), were pooled using a random-effect model. This meta-analysis has been registered on Prospero (ID: CRD42022344072).
RESULTS: A total of 35 studies with 28,756 patients were included. Pooled estimates revealed an increased incidence of primary outcomes; in-hospital all-cause mortality (RR = 3.52; 95% CI = 2.93-4.24), long-term all-cause mortality (HR = 1.07; 95% CI = 1.00-1.14), (RR = 3.32; 95% CI = 2.57-4.30); in-hospital cardiovascular mortality (RR = 2.66; 95% CI = 2.04-3.48), long-term cardiovascular mortality (RR = 6.67; 95% CI = 4.06-10.95); in-hospital major adverse cardiovascular events (MACE) (RR = 1.31; 95% CI = 1.17-1.46), long-term MACE (RR = 2.92; 95% CI = 2.16-3.94); length of hospital stay (WMD = 0.60 days; 95% CI = 0.40-0.79) in patients with high NLR compared to those with a low NLR.
CONCLUSIONS: NLR might be a valuable tool for prognostication (in-hospital) and stratification of patients with STEMI who underwent PCI.

Although the link between hepatic steatosis and lung function has been confirmed, the focus has largely been on central airways. The association between hepatic steatosis and increased peripheral airway resistance has not yet been explored. Hepatic steatosis and increased peripheral resistance are connected with immunity dysregulation. High neutrophil-to-lymphocyte ratio (NLR) and low lymphocyte-to-monocyte ratio (LMR) have been recognized as indicators of immunity dysregulation. In this study, the association between hepatic steatosis and increased peripheral airway resistance was evaluated, and the effect of immunity dysregulation (high NLR/low LMR) on the increased peripheral airway resistance among patients with hepatic steatosis was explored. In this retrospective study, chest or abdomen CT scans and spirometry/impulse oscillometry (IOS) from 2018 to 2019 were used to identify hepatic steatosis and increased central/peripheral airway resistance in patients. Among 1391 enrolled patients, 169 (12.1%) had hepatic steatosis. After 1:1 age and abnormal ALT matching was conducted, clinical data were compared between patients with and without hepatic steatosis. A higher proportion of patients with hepatic steatosis had increased peripheral airway resistance than those without hepatic steatosis (52.7% vs 40.2%, P = .025). Old age, high body mass index, history of diabetes, and high NLR/low LMR were significantly correlated with increased peripheral airway resistance. The presence of hepatic steatosis is associated with increased peripheral airway. High NLR/low LMR is an independent associated factor of increased peripheral airway resistance in patients with hepatic steatosis. It is advisable for patients with hepatic steatosis to regularly monitor their complete blood count/differential count and undergo pulmonary function tests including IOS.

Despite the observed decrease in liver fat associated with metabolic-associated fatty liver disease (MAFLD) in mice following fecal microbiota transplantation, the clinical effects and underlying mechanisms of washed microbiota transplantation (WMT), a refined method of fecal microbiota transplantation, for the treatment of MAFLD remain unclear. In this study, both patients and mice with MAFLD exhibit an altered gut microbiota composition. WMT increases the levels of beneficial bacteria, decreases the abundance of pathogenic bacteria, and reduces hepatic steatosis in MAFLD-affected patients and mice. Downregulation of the liver-homing chemokine receptor CXCR6 on ILC3s results in an atypical distribution of ILC3s in patients and mice with MAFLD, characterized by a significant reduction in ILC3s in the liver and an increase in ILC3s outside the liver. Moreover, disease severity is negatively correlated with the proportion of hepatic ILC3s. These hepatic ILC3s demonstrate a mitigating effect on hepatic steatosis through the release of IL-22. Mechanistically, WMT upregulates CXCR6 expression on ILC3s, thereby facilitating their migration to the liver of MAFLD mice via the CXCL16/CXCR6 axis, ultimately contributing to the amelioration of MAFLD. Overall, these findings highlight that WMT and targeting of liver-homing ILC3s could be promising strategies for the treatment of MAFLD.

OBJECTIVE: Systemic inflammation has been implicated in the development and progression of cancer. Inflammatory markers have been identified as prognostic indicators in numerous malignancies. This study explored the prognostic relevance of the initial and postoperative neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) on relapse-free survival (RFS) and overall survival (OS) in patients with soft-tissue sarcoma (STS) who underwent curative resection.
METHODS: We included 89 patients with STS who underwent extensive and radical resection at the Kyungpook National University Chilgok Hospital between 2004 and 2018. Kaplan-Meier curves for RFS and OS were calculated using multivariate Cox proportional models.
RESULTS: A total of 67 (75.3%) patients demonstrated a high initial NLR (≥4.1) and 65 (75.3%) showed a high initial PLR (≥231). In the univariate and multivariate analyses, an elevated initial PLR ratio was significantly associated with a decreased RFS (p=0.017) and OS (p=0.003). Patients with a high PLR (PLR >231) had a median RFS of 24 months, whereas those with a low PLR (PLR ≤231) had a median RFS of 96 months. The median OS was 50 and 298 months for the high PLR and low PLR groups, respectively. Furthermore, a high postoperative PLR ratio was associated with a decreased RFS (p=0.001) and OS (p=0.038).
CONCLUSIONS: Preoperative and postoperative PLR ratio can be used as a cost-effective prognostic marker for oncologic outcomes in patients with STS who undergo surgery.

Innate lymphoid cells (ILCs) and adaptive T lymphocytes promote tissue homeostasis and protective immune responses. Their production depends on the transcription factor GATA3, which is further elevated specifically in ILC2s and T helper 2 cells to drive type-2 immunity during tissue repair, allergic disorders, and anti-helminth immunity. The control of this crucial up-regulation is poorly understood. Using CRISPR screens in ILCs we identified previously unappreciated myocyte-specific enhancer factor 2d (Mef2d)-mediated regulation of GATA3-dependent type-2 lymphocyte differentiation. Mef2d-deletion from ILC2s and/or T cells specifically protected against an allergen lung challenge. Mef2d repressed Regnase-1 endonuclease expression to enhance IL-33 receptor production and IL-33 signaling and acted downstream of calcium-mediated signaling to translocate NFAT1 to the nucleus to promote type-2 cytokine-mediated immunity.

UNASSIGNED: Anti-Thymocyte Globulin (ATG) is a cornerstone in immune suppression for solid organ transplantation. The treatment is a delicate balance between complications arising from over-immunosuppression such as infections and cancer versus rejection stemming from under-immunosuppression. CD3+ T-lymphocyte measurements are frequently employed for treatment monitoring. However, this analysis is costly and not always accessible. The aim of this study was to investigate whether the total count of lymphocytes could replace CD3+ T-lymphocyte measurements based on data from our transplantation center combined with a review of the literature. The hypothesis was that the total lymphocyte count could serve as a diagnostic surrogate marker for CD3+ T-lymphocytes.
UNASSIGNED: A retrospective cohort study was conducted, including patients who underwent kidney and/or a pancreas transplantation and received ATG as induction therapy or for rejection treatment. The inclusion criterium was that the total lymphocyte count and CD3+ T-lymphocyte measurements were measured simultaneously on the same day. Additionally, PubMed and Embase were searched up to 18/10/2023 for published studies on solid organ transplantation, ATG, T-lymphocytes, lymphocyte count, and monitoring. In the retrospective cohort study, a total of 91 patients transplanted between 2016 and 2023, with 487 samples, were included.
UNASSIGNED: Total lymphocyte counts below 0.3 x 109/L had a high sensitivity (86%) as a surrogate marker of CD3+ T-lymphocytes below 0.05 x 109/L, but the specificity was low (52%) for total lymphocyte counts above 0.3 x 109/L as a surrogate marker for CD3+ T-lymphocytes above 0.05 x 109/L. A review of the literature identified seven studies comparing total lymphocyte counts and CD3+ T-lymphocytes in ATG monitoring. These studies supported the use of a low total lymphocyte count as a surrogate marker for CD3+ T-lymphocytes and an indicator to omit ATG treatment. However, there was no consensus regarding high total lymphocyte counts as an indicator for continued treatment.
UNASSIGNED: Results supports that the total lymphocyte count can be used to omit ATG treatment when below 0.3 x 109/L whereas the CD3+ T-lymphocyte analysis should be reserved for higher total lymphocyte counts to avoid ATG overtreatment.

Background and objectives: Colorectal cancer is a major global health concern, with a significant increase in morbidity and mortality rates associated with metastatic stages. This study investigates the prognostic significance of various clinical and laboratory parameters in patients with metastatic CRC. Materials and Methods: A retrospective cohort of 188 CRC patients with hepatic metastasis from the OncoHelp Association in Timisoara was analyzed from January 2016 to March 2023. Data on demographics, clinical characteristics, and biomarkers, such as lymphocyte counts, as well as various inflammation indices, were examined. Statistical analyses included univariate and multivariate logistic regression, Kaplan-Meier survival analysis, and ROC curve assessments. Results: Our findings indicate significant associations between survival outcomes and several biomarkers. Higher BMI and lymphocyte counts were linked with better survival rates, while higher values of Neutrophil-Hemoglobin-Lymphocyte (NHL) score, Neutrophil-Lymphocyte Ratio (NLR), Platelet-Lymphocyte Ratio (PLR), and Systemic Immune-Inflammation Index (SII) were predictors of poorer outcomes. Notably, the presence of hepatic metastasis at diagnosis was a critical factor, significantly reducing overall survival. Conclusions: The study has expanded the current understanding of prognostic factors in CRC, advocating for a multi-dimensional approach to prognostic evaluations. This approach should consider not only the traditional metrics such as tumor stage and histological grading but also incorporate a broader spectrum of biomarkers. Future studies should aim to validate these findings and explore the integration of these biomarkers into routine clinical practice, enhancing the precision of prognostic assessments and ultimately guiding more personalized treatment strategies for CRC patients.

Transient Receptor Potential Ankyrin 1 (TRPA1) is a non-selective cation channel involved in sensitivity to a plethora of irritating agents and endogenous mediators of oxidative stress. TRPA1 influences neuroinflammation and macrophage and lymphocyte functions, but its role is controversial in immune cells. We reported earlier a detectable, but orders-of-magnitude-lower level of Trpa1 mRNA in monocytes and lymphocytes than in sensory neurons by qRT-PCR analyses of cells from lymphoid organs of mice. Our present goals were to (a) further elucidate the expression of Trpa1 mRNA in immune cells by RNAscope in situ hybridization (ISH) and (b) test the role of TRPA1 in lymphocyte activation. RNAscope ISH confirmed that Trpa1 transcripts were detectable in CD14+ and CD4+ cells from the peritoneal cavity of mice. A selective TRPA1 agonist JT010 elevated Ca2+ levels in these cells only at high concentrations. However, a concentration-dependent inhibitory effect of JT010 was observed on T-cell receptor (TcR)-induced Ca2+ signals in CD4+ T lymphocytes, while JT010 neither modified B cell activation nor ionomycin-stimulated Ca2+ level. Based on our present and past findings, TRPA1 activation negatively modulates T lymphocyte activation, but it does not appear to be a key regulator of TcR-stimulated calcium signaling.