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      Comparison of serum cytokines and chemokines levels and clinical significance in patients with pemphigus vulgaris—A retrospective study

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          Abstract

          In this study, we aimed to examine the relationship between the serum cytokine levels of patients with pemphigus vulgaris (PV) and the Pemphigus Disease Area Index (PDAI), along with the presence of anti‐desmoglein (Dsg) 1 antibody, anti‐Dsg3 antibody and co‐infection among patients with pemphigus vulgaris. This retrospective study included 62 PV patients and 59 healthy individuals who attended the Second Affiliated Hospital of Kunming Medical University from November 2014 to November 2022. The serum concentrations of cytokines and chemokines were assessed using the Luminex 200 System (a high‐throughput cytokine detection method). Additionally, anti‐Dsg1 and anti‐Dsg3 antibodies were determined through enzyme‐linked immunosorbent assay, while disease severity was evaluated using the PDAI scoring system. The PV group exhibited elevated levels of Th1 cytokines (such as interleukin (IL)‐1RA, IL‐1β, IL‐2, IL‐12p70, GM‐CSF, TNF‐α, IL‐18, IFN‐γ), Th2 cytokines (IL‐5, IL‐10, IL‐13) and Th17/Th22‐related cytokines (IL‐17A, IL‐22) compared to the healthy control group ( p < 0.05). Conversely, the levels of chemokines (macrophage inflammatory protein‐1 alpha (MIP‐1α), stromal cell‐derived factor‐1 alpha (SDF‐1α), interferon‐inducible protein‐10 (IP‐10), Regulated on Activation in Normal T‐Cell Expressed And Secreted (RANTES), growth‐regulated on‐gene‐alpha (GRO‐α), MIP‐1β) and Th2 (IL‐31) were lower in the PV group compared to the healthy control group ( p < 0.05). No significant differences were observed in other cytokines and chemokines ( p > 0.05). Additionally, IL‐7, IFN‐γ, IL‐18 and GRO‐α showed positive correlations with PDAI, IL‐6 correlated positively with anti‐Dsg3 antibody levels, and IL‐12p70, IL‐18, and IFN‐γ correlated positively with anti‐Dsg1 antibody levels. Furthermore, IL‐15 exhibited a positive association with skin infections. PV patients have elevated levels of various cytokines and chemokines, and there are different degrees of elevation in cytokines and chemokines associated with the activation of various T cell subsets. PDAI and the Dsg1 antibody levels are mainly related to the Th1‐related cytokines.

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          More Than Just Attractive: How CCL2 Influences Myeloid Cell Behavior Beyond Chemotaxis

          Monocyte chemoattractant protein-1 (MCP-1/CCL2) is renowned for its ability to drive the chemotaxis of myeloid and lymphoid cells. It orchestrates the migration of these cell types both during physiological immune defense and in pathological circumstances, such as autoimmune diseases including rheumatoid arthritis and multiple sclerosis, inflammatory diseases including atherosclerosis, as well as infectious diseases, obesity, diabetes, and various types of cancer. However, new data suggest that the scope of CCL2's functions may extend beyond its original characterization as a chemoattractant. Emerging evidence shows that it can impact leukocyte behavior, influencing adhesion, polarization, effector molecule secretion, autophagy, killing, and survival. The direction of these CCL2-induced responses is context dependent and, in some cases, synergistic with other inflammatory stimuli. The involvement of CCL2 signaling in multiple diseases renders it an interesting therapeutic target, although current targeting strategies have not met early expectations in the clinic. A better understanding of how CCL2 affects immune cells will be pivotal to the improvement of existing therapeutic approaches and the development of new drugs. Here, we provide an overview of the pleiotropic effects of CCL2 signaling on cells of the myeloid lineage, beyond chemotaxis, and highlight how these actions might help to shape immune cell behavior and tumor immunity.
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            IL-12 family cytokines: immunological playmakers.

            The interleukin 12 (IL-12) family is unique in having the only heterodimeric cytokines, including IL-12, IL-23, IL-27 and IL-35. This feature endows these cytokines with a unique set of connections and functional interactions not shared by other cytokine families. Despite sharing many structural features and molecular partners, cytokines of the IL-12 family mediate surprisingly diverse functional effects. Here we discuss the unique and unusual structural and functional characteristics of this cytokine family. We outline how cells might interpret seemingly similar cytokine signals to give rise to the diverse functional outcomes that characterize this cytokine family. We also discuss the therapeutic implications of this complexity.
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              Interleukin-18 regulates both Th1 and Th2 responses.

              Although interleukin-18 is structurally homologous to IL-1 and its receptor belongs to the IL-1R/Toll-like receptor (TLR) superfamily, its function is quite different from that of IL-1. IL-18 is produced not only by types of immune cells but also by non-immune cells. In collaboration with IL-12, IL-18 stimulates Th1-mediated immune responses, which play a critical role in the host defense against infection with intracellular microbes through the induction of IFN-gamma. However, the overproduction of IL-12 and IL-18 induces severe inflammatory disorders, suggesting that IL-18 is a potent proinflammatory cytokine that has pathophysiological roles in several inflammatory conditions. IL-18 mRNA is expressed in a wide range of cells including Kupffer cells, macrophages, T cells, B cells, dendritic cells, osteoblasts, keratinocytes, astrocytes, and microglia. Thus, the pathophysiological role of IL-18 has been extensively tested in the organs that contain these cells. Somewhat surprisingly, IL-18 alone can stimulate Th2 cytokine production as well as allergic inflammation. Therefore, the functions of IL-18 in vivo are very heterogeneous and complicated. In principle, IL-18 enhances the IL-12-driven Th1 immune responses, but it can also stimulate Th2 immune responses in the absence of IL-12.
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                Author and article information

                Contributors
                (View ORCID Profile)
                Journal
                Experimental Dermatology
                Experimental Dermatology
                Wiley
                0906-6705
                1600-0625
                September 2024
                September 09 2024
                September 2024
                : 33
                : 9
                Affiliations
                [1 ] Department of Dermatology The Second Affiliated Hospital of Kunming Medical University Kunming Yunnan China
                Article
                10.1111/exd.15173
                39246287
                4d01cef6-465e-43f2-928c-5c9299545d38
                © 2024

                http://onlinelibrary.wiley.com/termsAndConditions#vor

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