CCL27: Novel Cytokine with Potential Role in Pathogenesis of Multiple Sclerosis

Khaiboullina, Svetlana F.; Gumerova, Aigul R.; Khafizova, Irina F.; Martynova, Ekaterina; Lombardi, Vincent; Bellusci, Saverio; Rizvanov, Albert A.

doi:10.1155/2015/189638

Cited by 22 publications

(19 citation statements)

References 57 publications

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“…We have previously shown that serum levels of CCL27 are upregulated in subjects with MS (55). CCL27 was two times higher in the serum of acute MS subjects and remained upregulated in the later stages of the disease.…”

Section: Memory Cla+ T Cells In Msmentioning

confidence: 99%

The Skin–Brain Connection Hypothesis, Bringing Together CCL27-Mediated T-Cell Activation in the Skin and Neural Cell Damage in the Adult Brain

et al. 2017

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Recent discovery of an association of low serum melatonin levels with relapse in multiple sclerosis (MS) opens a new horizon in understanding the pathogenesis of this disease. Skin is the main organ for sensing seasonal changes in duration of sunlight exposure. Level of melatonin production is dependent on light exposure. The molecular mechanisms connecting peripheral (skin) sensing of the light exposure and developing brain inflammation (MS) have not been investigated. We hypothesize that there is a connection between the reaction of skin to seasonal changes in sunlight exposure and the risk of MS and that seasonal changes in light exposure cause peripheral (skin) inflammation, the production of cytokines, and the subsequent inflammation of the brain. In skin of genetically predisposed individuals, cytokines attract memory cutaneous lymphocyte-associated antigen (CLA+) T lymphocytes, which then maintain local inflammation. Once inflammation is resolved, CLA+ lymphocytes return to the circulation, some of which eventually migrate to the brain. Once in the brain these lymphocytes may initiate an inflammatory response. Our observation of increased CC chemokine ligand 27 (CCL27) in MS sera supports the involvement of skin in the pathogenesis of MS. Further, the importance of our data is that CCL27 is a chemokine released by activated keratinocytes, which is upregulated in inflamed skin. We propose that high serum levels of CCL27 in MS are the result of skin inflammation due to exposure to seasonal changes in the sunlight. Future studies will determine whether CCL27 serum level correlates with seasonal changes in sunlight exposure, MS exacerbation, and skin inflammation.

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Section: Memory Cla+ T Cells In Msmentioning

confidence: 99%

The Skin–Brain Connection Hypothesis, Bringing Together CCL27-Mediated T-Cell Activation in the Skin and Neural Cell Damage in the Adult Brain

et al. 2017

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“…Among them, RRMS accounts for the majority of patients (about 80%) [87]. The hallmark of MS is leukocyte infiltration of brain tissue and subsequent axonal injury, demyelination inflammation and the formation of sclerosing plaques [54].…”

Section: Introductionmentioning

confidence: 99%

The role of chemokines and chemokine receptors in multiple sclerosis

Cui

Chu

Chen

2020

International Immunopharmacology

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Multiple sclerosis (MS) is a chronic inflammatory disease that is characterized by leukocyte infiltration and subsequent axonal damage, demyelinating inflammation, and formation of sclerosing plaques in brain tissue. The results of various studies in patients indicate that autoimmunity and inflammation make an important impact on the pathogenesis of MS. Chemokines are key mediators of inflammation development and cell migration, mediating various immune cell responses, including chemotaxis and immune activation, and are important in immunity and inflammation, therefore we focus on chemokines and their receptors in multiple sclerosis. In this article, we summarize the study of the role of prominent chemokines and their receptors in MS patients and MS animal modelsand discuss their potential significance in inflammatory injury and repair of MS. We have also summarized the progress in the treatment of multiple sclerosis antagonists in recent years with chemokine receptors as targets.

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“…We have shown differential activation of cytokines in CSF and serum of MS patients, where the leading role of Th1 lymphocytes in CNS MS pathogenesis was supported. Also, the upregulation of CCL27 was demonstrated in serum and CSF of MS, suggesting the role of this cytokine in neuroinflammation [ 6 ]. Although proinflammatory cytokines are commonly detected in CSF of MS, data remain limited.…”

Section: Introductionmentioning

confidence: 99%

Serum and Cerebrospinal Fluid Cytokine Biomarkers for Diagnosis of Multiple Sclerosis

Martynova

Goyal

Johri

et al. 2020

Mediators of Inflammation

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Background. Multiple sclerosis (MS) is a chronic debilitating disorder characterized by persisting damage to the brain caused by autoreactive leukocytes. Leukocyte activation is regulated by cytokines, which are readily detected in MS serum and cerebrospinal fluid (CSF). Objective. Serum and CSF levels of forty-five cytokines were analyzed to identify MS diagnostic markers. Methods. Cytokines were analyzed using multiplex immunoassay. ANOVA-based feature and Pearson correlation coefficient scores were calculated to select the features which were used as input by machine learning models, to predict and classify MS. Results. Twenty-two and twenty cytokines were altered in CSF and serum, respectively. The MS diagnosis accuracy was ≥92% when any randomly selected five of these biomarkers were used. Interestingly, the highest accuracy (99%) of MS diagnosis was demonstrated when CCL27, IFN-γ, and IL-4 were part of the five selected cytokines, suggesting their important role in MS pathogenesis. Also, these binary classifier models had the accuracy in the range of 70-78% (serum) and 60-69% (CSF) to discriminate between the progressive (primary and secondary progressive) and relapsing-remitting forms of MS. Conclusion. We identified the set of cytokines from the serum and CSF that could be used for the MS diagnosis and classification.

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CCL27: Novel Cytokine with Potential Role in Pathogenesis of Multiple Sclerosis

Cited by 22 publications

References 57 publications

The Skin–Brain Connection Hypothesis, Bringing Together CCL27-Mediated T-Cell Activation in the Skin and Neural Cell Damage in the Adult Brain

The Skin–Brain Connection Hypothesis, Bringing Together CCL27-Mediated T-Cell Activation in the Skin and Neural Cell Damage in the Adult Brain

The role of chemokines and chemokine receptors in multiple sclerosis

Serum and Cerebrospinal Fluid Cytokine Biomarkers for Diagnosis of Multiple Sclerosis

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