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Last update 08 May 2025

CCL25

Last update 08 May 2025

Basic Info

Synonyms

C-C motif chemokine 25, C-C motif chemokine ligand 25, CCL25

+ [6]

Introduction

Potentially involved in T-cell development. Recombinant protein shows chemotactic activity on thymocytes, macrophages, THP-1 cells, and dendritics cells but is inactive on peripheral blood lymphocytes and neutrophils. Binds to CCR9. Isoform 2 is an antagonist of isoform 1. Binds to atypical chemokine receptor ACKR4 and mediates the recruitment of beta-arrestin (ARRB1/2) to ACKR4.

Drugs associated with CCL25

HG-1094

Target

CCL25

Mechanism

CCL25 modulators

Active Org.-

Originator Org.

Human Genome Sciences, Inc.

Active Indication-

Inactive Indication

Immune System Diseases [+1]

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with CCL25

100 Translational Medicine associated with CCL25

0 Patents (Medical) associated with CCL25

552

Literatures (Medical) associated with CCL25

01 Aug 2025·Brain, Behavior, and Immunity

CCL25 in the cerebrospinal fluid is negatively correlated with fatigue in chronic pain patients

Article

Author: Svensson, Camilla I ; Kultima, Kim ; Kosek, Eva ; Bjurström, Martin F ; Rosenström, Alexander H C ; Berg, Svante ; Farinotti, Alex Bersellini ; Ahmed, Aisha Siddiqah

BACKGROUND AND AIMChronic pain is often accompanied by other symptoms such as fatigue and sleep disturbance, and these symptoms all correlate with neuroimmune activation. However, their relation to one another on a neuroimmune axis remains elusive. Based on a recent review, cytokines in the cerebrospinal fluid (CSF) seem to be generally upregulated in patients with chronic pain compared to controls, disregarding pain type. Some of these have the possilibity of altering blood-brain barrier (BBB) permeability. Therefore, cytokine levels in serum and CSF, as well as BBB permeability, were measured in a cohort of patients suffering from either degenerative disc disease (DDD), lumbar disc herniation (LDH) or osteoarthritis (OA). In this exploratory study, we were interested in whether cytokines in the serum or CSF are associated with sleep disturbance or fatigue, with special consideration of the effect of BBB permeability, and whether functional clusters can be found among these cytokines.METHODOne-hundred-twenty patients with DDD/LDH/OA, all awaiting surgery, were included. Blood and CSF were collected on the day of surgery. Pain was measured with a visual analog scale 0-100 mm, sleep disturbance was assessed using Pittsburgh Sleep Quality Index (PSQI), and fatigue was measured using the Multidimensional Fatigue Inventory (MFI). A 92-protein multiplex panel (OLINK, Sweden) was used to analyze cytokine expression in serum and CSF, respectively. CSF-serum albumin quotient was measured using ELISA. Non-parametric statistics were used for univariate analyses, and a false discovery rate (FDR) < 0.10 was considered statistically significant. Bonferroni correction was applied to all multivariable protein analyses to obtain conservative effect estimates.MAIN RESULTSThere was an association between BBB permeability and serum-CSF dynamics: thirty-one cytokines showed significant CSF-serum correlation, and BBB permeability was significantly correlated to the quotients of 35 cytokines and to the CSF levels of 11 cytokines. Several cytokines were negatively correlated to both pain at rest and general fatigue. No correlations were found between sleep disturbance and cytokines. Network analyses of serum and CSF cytokines that were correlated with fatigue revealed functional clusters in both compartments. Anxiety, depression, and pain during rest were important regressors for sleep disturbance with an R² = 0.41. In addition to depression and pain during rest, CSF levels of CCL25 was a significant regressor regarding general fatigue, with an R² = 0.47.DISCUSSION AND CONCLUSIONIn this exploratory study of immune profiles in chronic pain cohorts awaiting surgery, the importance of BBB dynamics on serum-CSF cytokine dynamics, and to a lesser extent on central levels of cytokines, is highlighted. Surprisingly, there were no associations between any cytokines in serum or CSF and sleep disturbance, despite a high prevalence of clinically significantly disturbed sleep. In contrast, several associations between general fatigue and cytokine levels in both serum and CSF were found. Cytokines of note are CXCL11 and CCL25 in the CSF, especially because of their direct functional association. CXCL11 has been found to exert neuroprotective effects in animal models, while CCL25 is known as a proinflammatory cytokine and is the only cytokine to fall out as a significant negative contributor to degree of fatigue. While causality cannot be addressed, the negative correlation between CCL25 and fatigue in both univariate and multivariate analyses implies that neuroimmune activity might have an ameliorating effect on the degree of fatigue. This study further adds to existing evidence that centrally acting cytokines are associated with severity of symptomatology, and highlights that pain and fatigue seem to have slightly different cytokine profiles. Sleep disturbance needs to be further addressed, ideally using both subjective and objective assessment methods. CCL25 and CXCL11 are interesting biomarkers for future research on pain and associated symptoms.

01 May 2025·World Neurosurgery

Causal Association Between Inflammatory Proteins, Inflammatory Cells, and Cauda Equina Syndrome: A Two-Sample Mendelian Randomization

Article

Author: Sun, Kaiqiang ; Sun, Xiaofei ; Shi, Jiangang ; Han, Linhui ; Wang, Yuan ; Xing, Jianpeng ; Zhang, Bin ; Kong, Qingjie ; Wang, Jinyu

BACKGROUNDRecent studies have shown that inflammation plays a crucial role in the progression of cauda equina syndrome (CES). However, the exact cause-and-effect relationship between them is still unclear.METHODSWe used CES data from the FinnGen genome-wide association study (GWAS), containing 329 cases and 408,351 control patients. Inflammatory proteins data were obtained from a large scale GWAS of 14,828 European ancestry participants, and inflammatory cells data were obtained from a GWAS summary of 3757 Sardinians. We chose inverse variance weighted as the main method and the Cochrane Q test to assess heterogeneity in the results. The MR-Egger intercept test and MR pleiotropy residual sum and outliers test were used to evaluate the horizontal pleiotropy, and sensitivity analysis was performed by leave-one-out analysis.RESULTSWe examined robust associations between inflammatory proteins, inflammatory cells, and CES using Mendelian randomization. Two inflammatory proteins and 12 inflammatory cells were found as risk factors for CES: IL-8 and PD-L1; and basophil plasmacytoid dendritic cell, CD86+plasmacytoid dendritic cell, CD62L-plasmacytoid dendritic cell, CD39+secreting Treg, IgD+CD38-B cell, switched memory B cell, IgD+CD24+B cell, CD62L+dendritic cell, CD4+T cell, γδ T cell, and CD33dim HLA DR-myeloid cell. Two inflammatory proteins and 7 inflammatory cells were found as protective factors for CES: IL-10RA and CCL25; and transitional B cell, terminal differentiation double negative T cell, CD28-CD127-CD25++CD8br T cell, IgD+CD38br B cell, CD28+CD45RA-CD8br Treg, IgD+CD38-naive B cell, and granulocyte. Heterogeneity and pleiotropy analysis confirmed the reliability of the results. Our study reveals the causal relationship between inflammatory proteins, inflammatory cells, and CES, offering new insights for the development of future therapeutic drugs and early warning indicators.CONCLUSIONSOur findings extend genetic research to causal analysis between inflammatory proteins, cells, and CES. We found 2 proteins and 12 cells as risk factors and 2 proteins and 7 cells as protective factors. Further investigations are needed to verify whether these inflammation markers can be used to prevent or treat CES.

01 May 2025·International Journal of Biological Macromolecules

Carnitine palmitoyltransferase 2 as a novel prognostic biomarker and immunoregulator in colorectal cancer

Article

Author: Ke, Yuan ; Cui, Hong-Yong ; Yang, Ting ; Fan, Xin-Yu ; Huo, Fei ; Li, Ling ; Fan, Jing ; Feng, Le-Le ; Zhang, Jia-Jia ; Fu, Xin ; Wang, Hao ; Shi, Ying ; Chen, Zhi-Nan ; Liang, Xue ; Tian, Ruo-Fei

BACKGROUNDMetabolic interventions are critical for enhancing immunotherapy efficacy, but reliable metabolic targets remain absent for colorectal cancer (CRC). This study aims to investigate the interplay between metabolic and immunological factors in CRC, identify metabolic immunoregulatory molecules, and propose targets for prognostic and therapeutic applications.METHODSImmune infiltration and metabolic pathways in CRC were analyzed using CIBERSORT and gene set variation analyses. Cox regression identified survival-related metabolic genes, forming a metabolic-related gene prognostic index (MRGPI), which was validated through survival analysis, timeROC, GSEA, CIBERSORT, and TIDE. Hub genes in the MRGPI were assessed using enrichment and co-expression network analyses. The expression of carnitine palmitoyltransferase 2 (CPT2) was validated through multiplex immunofluorescence of tissue microarrays. While its role was examined by western blot, CCK-8 assay, flow cytometry, qRT-PCR, Elisa, chemotaxis assays, etc. RESULTS: Fatty acid oxidation (FAO) pathways were significantly altered in CRC and correlated with immune cell infiltration and patient survival. The MRGPI, constructed from five survival-related metabolic genes, demonstrated strong prognostic and immunotherapeutic predictive value. Moreover, CPT2, a key hub gene in the MRGPI, whose lower expression in plasma cells predicts unfavorable patients' survival and could be an independent prognostic indicator, while its knockout in tumor cells significantly increases the infiltrating levels of CD8⁺ T cells via promoting the release of CCL25.CONCLUSIONThe FAO-dominated MRGPI is a promising biomarker for predicting patient outcomes and immunotherapy response. CPT2 holds potential as a prognostic marker and therapeutic target for CRC metabolic immunotherapy.

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CCL25

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