Bi-allelic variants in DNHD1 cause flagellar axoneme defects and asthenoteratozoospermia in humans and mice.

Asthenoteratozoospermia, defined as reduced sperm motility and abnormal sperm morphology, is a disorder with considerable genetic heterogeneity. Although previous studies have identified several asthenoteratozoospermia-associated genes, the etiology remains unknown for the majority of affected men. Here, we performed whole-exome sequencing on 497 unrelated men with asthenoteratozoospermia and identified DNHD1 bi-allelic variants from eight families (1.6%). All detected variants were predicted to be deleterious via multiple bioinformatics tools. Hematoxylin and eosin (H&E) staining revealed that individuals with bi-allelic DNHD1 variants presented striking abnormalities of the flagella; transmission electron microscopy (TEM) further showed flagellar axoneme defects, including central pair microtubule (CP) deficiency and mitochondrial sheath (MS) malformations. In sperm from fertile men, DNHD1 was localized to the entire flagella of the normal sperm; however, it was nearly absent in the flagella of men with bi-allelic DNHD1 variants. Moreover, abundance of the CP markers SPAG6 and SPEF2 was significantly reduced in spermatozoa from men harboring bi-allelic DNHD1 variants. In addition, Dnhd1 knockout male mice (Dnhd1‒/‒) exhibited asthenoteratozoospermia and infertility, a finding consistent with the sperm phenotypes present in human subjects with DNHD1 variants. The female partners of four out of seven men who underwent intracytoplasmic sperm injection therapy subsequently became pregnant. In conclusion, our study showed that bi-allelic DNHD1 variants cause asthenoteratozoospermia, a finding that provides crucial insights into the biological underpinnings of this disorder and should assist with counseling of affected individuals.

Spark Plasma Sintering-Assisted Synthesis of Bi2Fe4O9/Bi25FeO40 Heterostructures with Enhanced Photocatalytic Activity for Removal of Antibiotics.

Bismuth ferrite-based heterojunction composites have been considered as promising visible-light responsive photocatalysts because of their narrow band gap structure; however, the synthetic methods reported in the literature were usually time-consuming. In this study, we report a facile and quick preparation of bismuth ferrite-based composites by the hydrothermal method, combined with spark plasma sintering (SPS), a technique that is usually used for the high-speed consolidation of powders. The result demonstrated that the SPS-assisted synthesized samples possess significant enhanced photoelectric and photocatalytic performance. Specifically, the SPS650 (sintered at the 650 °C for 5 min by SPS) exhibits a 1.5 times enhancement in the photocurrent density and a 3.8 times enhancement in the tetracycline hydrochloride photodegradation activity than the unmodified bismuth ferrite samples. The possible influence factors of SPS on photoelectric and photocatalytic performance of bismuth ferrite-based composites were discussed carefully. This study provides a feasible method for the facile and quick synthesis of a highly active bismuth ferrite-based visible-light-driven photocatalyst for practical applications.

Catalytic Reductive Cross Coupling and Enantioselective Protonation of Olefins to Construct Remote Stereocenters for Azaarenes.

A novel enantioselective protonation protocol that is triggered by reductive cross coupling of olefins is reported. When under cooperative photoredox and chiral hydrogen-bonding catalytic conditions and using a terminal reductant, various α-branched vinylketones with diverse vinylazaarenes could provide important enantioenriched azaarene derivatives containing tertiary stereocenters at their remote δ-position with high yields and enantioselectivities. This reaction system is also suitable for α-branched vinylazaarenes, thus successfully assembling elusive 1,4-stereocenters. The convenient late-stage modifications of products, especially the formation of remote ε-tertiary and ε-heteroquaternary carbon stereocenters, further highlight the important synthetic value of this method. Control experiments and density functional theory (DFT) calculations were conducted to elucidate the plausible reaction mechanism and origins of regioselectivity and stereoselectivity.

Black carp TRADD suppresses MAVS/IFN signaling during the innate immune activation.

Tumor necrosis factor receptor 1 (TNFR1) associated death domain protein (TRADD) is a pivotal adaptor in TNF signaling pathway and up-regulates MAVS/IFN signaling pathway in human and mammal. However, the role of TRADD in teleost fish remains obscure. To reveal the function of teleost TRADD in the innate immune response, the TRADD homologue (bcTRADD) of black carp (Mylopharyngodon piceus) has been cloned and the function of bcTRADD is investigated in this study, which shares similar functional domain to its mammalian counterpart. bcTRADD mRNA expression level increased in response to different stimuli, including LPS, poly (I:C) and virus infection in host cells. bcTRADD activated the transcriptional activity of NF-κB promoter in the reporter assay; however, showed hardly any effect on the transcriptional activity of IFN promoter. It was interesting that black carp mitochondria antiviral signaling protein (bcMAVS)-activated IFN promoter transcription were dramatically depressed by bcTRADD and the C-terminal death domain of bcTRADD was indispensable for its regulation of bcMAVS. Accordingly, the plaque assay result showed that EPC cells co-expressing bcMAVS and bcTRADD presented much attenuated antiviral activity than EPC cells expressing bcMAVS alone. Knockdown of bcTRADD slightly promoted the antiviral ability of the host cells against SVCV. The current data support the conclusion that bcTRADD suppresses MAVS-mediated antiviral signaling, which is different to its mammalian counterpart.

Black carp TRAFD1 restrains MAVS-mediated antiviral signaling during the innate immune activation.

TRAFD1 negatively regulates TLR and RLR signaling in human and mammal; however, its role in teleost fish remains unknown. In this paper, the TRAFD1 homologue has been cloned and characterized from black carp (Mylopharyngodon piceus). Black carp TRAFD1 (bcTRAFD1) consists of 567 amino acids and shows low similarity to that of mammalian TRAFD1, which has been identified as a cytosolic protein through immunofluorescence staining. When co-expressed with bcTRAFD1, the IFN promoter-inducing ability of black carp MAVS (bcMAVS) was obviously dampened in the luciferase reporter assay. Accordingly, bcMAVS-mediated antiviral activity against grass carp reovirus (GCRV) and spring viremia of carp virus (SVCV) was potently repressed by bcTRAFD1 in plaque assay. And the co-immunoprecipitation assay between bcTRAFD1 and bcMAVS has identified the association between these two molecules. Thus, our data supports the conclusion that bcTRAFD1 interacts with bcMAVS and negatively regulates bcMAVS-mediated antiviral signaling during the innate immune activation, which sheds a light on the regulation of MAVS in teleost.

Black carp TAB1 up-regulates TAK1/IRF7/IFN signaling during the antiviral innate immune activation.

TAK1-binding protein 1 (TAB1) forms the protein complex with TAK1 and enhances its kinase activity in human and mammals. To elucidate the role of TAB1 in the innate immunity of teleost sfih, the TAB1 homologue of black carp (Mylopharyngodon piceus) (bcTAB1) has been cloned and characterized in this paper. bcTAB1 is composed of 498 amino acids and contains a typical PP2Cc domain like its mammalian counterpart. The transcription of bcTAB1 gene in vivo and ex vivo varied in response to different stimuli; and the immunofluorescence staining showed that bcTAB1 was distributed in both cytoplasm and nucleus of host cell. The reporter assay showed that neither bcTAB1-expression alone nor co-expression of bcTAB1 and bcTAK1 could activate the transcription of IFN in EPC cells. Accordingly, EPC cells expressing bcTAB1 or co-expressing bcTAB1 and bcTAK1 showed no improved antiviral activity against grass carp reovirus (GCRV) and spring viremia of carp virus (SVCV). However, EPC cells co-expressing bcTAB1, bcTAK1 and bcIRF7 showed fiercely increased IFN-inducing ability in reporter assay and obviously improved antiviral activity in plaque assay compared with EPC cells co-expressing bcTAK1 and bcIRF7. The subsequent co-immunoprecipitation assay identified that bcTAB1 associated with bcTAK1 but not interacted with bcIRF7. Based on our previous finding that bcTAK1 up-regulates bcIRF7-mediated IFN signaling during host innate immune activation, the data generated in this study support the conclusion that bcTAB1 interacts with bcTAK1 and boosts bcTAK1-activated bcIRF7/IFN signaling during host antiviral innate immune response against GCRV and SVCV.

Clinical characteristics of pyoderma gangrenosum: Case series and literature review.

BACKGROUND: Pyoderma gangrenosum (PG) is a neutrophilic skin disease characterized by recurrent painful cutaneous ulcers, often accompanied by inflammatory bowel disease, joint pain, and other systemic damage. This disease is relatively rare in clinical practice and its diagnosis and treatment are often delayed, leading to secondary infections in the skin lesions, prolonged disease course, and increased disease burden on patients. This study retrospectively analyzed the clinical characteristics and treatment strategies of patients with PG admitted to our hospital and conducted a literature review, in order to improve the understanding of the disease among clinical doctors, enable patients to receive better diagnosis and treatment, and ultimately improve patient prognosis. METHODS: Clinical data of patients diagnosed with PG and hospitalized in Beijing Chaoyang Hospital, Capital Medical University from January 2014 to December 2022 were retrospectively collected. The clinical manifestations, treatment strategies, efficacy, and disease outcomes were analyzed. RESULTS: A total of 14 patients, including 8 males and 6 females, aged 14 to 66 years, were included. Skin lesion types: 13 cases were ulcer-type, 1 case was pustule combined with ulcer-type, and the lower limbs were the most commonly affected areas. All the 14 patients presented with comorbidities. All patients were treated with glucocorticoids, with a daily dose equivalent to 20 to 100 mg prednisone and a median dose of 40 mg. Among them, 3 patients were treated with minocycline in combination, 1 patient was treated with mycophenolate mofetil 0.5 twice daily in combination, 1 patient was treated with cyclophosphamide 0.1 once daily in combination, and 1 patient was treated with thalidomide 0.1 every night in combination. CONCLUSION: PG is a relatively rare immune-related skin disease. Our small sample data analysis found that male PG is not uncommon in the Chinese population. Systemic glucocorticoids can quickly control the symptoms of PG in most patients with PG. In patients with poor efficacy or limited use of glucocorticoids, immunosuppressive drugs or novel targeted drugs such as biologics or small-molecule drugs should be used in combination as early as possible. Skin lesion care focuses on preventing infection, avoiding surgical debridement, and emphasizing pain management and the symptomatic treatment of comorbidities.

Oncogenic Roles of Laminin Subunit Gamma-2 in Intrahepatic Cholangiocarcinoma via Promoting EGFR Translation.

Intrahepatic cholangiocarcinoma (iCCA) is a highly lethal biliary epithelial cancer in the liver. Here, Laminin subunit gamma-2 (LAMC2) with important oncogenic roles in iCCA is discovered. In a total of 231 cholangiocarcinoma patients (82% of iCCA patients) across four independent cohorts, LAMC2 is significantly more abundant in iCCA tumor tissue compared to normal bile duct and non-tumor liver. Among 26.3% of iCCA patients, LAMC2 gene is amplified, contributing to its over-expression. Functionally, silencing LAMC2 significantly blocks tumor formation in orthotopic iCCA mouse models. Mechanistically, it promotes EGFR protein translation via interacting with nascent unglycosylated EGFR in the endoplasmic reticulum (ER), resulting in activated EGFR signaling. LAMC2-mediated EGFR translation also depends on its interaction with the ER chaperone BiP via their C-terminus. Together LAMC2 and BiP generate a binding "pocket" of nascent EGFR and facilitate EGFR translation. Consistently, LAMC2-high iCCA patients have poor prognosis in two iCCA cohorts. LAMC2-high iCCA cells are highly sensitive to EGFR tyrosine kinase inhibitors (TKIs) treatment both in vitro and in vivo. Together, these data demonstrate LAMC2 as an oncogenic player in iCCA by promoting EGFR translation and an indicator to identify iCCA patients who may benefit from available EGFR-targeted TKIs therapies.

Blastic Plasmacytoid Dendritic Cell Neoplasm with Lung Involvement and Cytopenia: A Case Report and a Literature Review.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a hostile cutaneous malignancy with dismal prognosis and unknown etiology with rarity. Most patients received traditional chemotherapy only has one year of median survival time. This article reports an 81-year-old male patient with BPDCN who presented with skin manifestations and was diagnosed with positive CD4, CD56, and CD123 immunohistochemical results. Systematic examination revealed lung involvement and cytopenia.

Merkel Cell Carcinoma on the Forearm: A Case Report and Literature Review.

Merkel cell carcinoma (MCC) is a rare cutaneous growth with aggressive nature. It mostly affects on the head and neck of white men aged 65 years old and immunosuppressed patients. Limited cases were reported in Asian patients. Loco-regional metastases with the regional lymph nodes involvement were common. The treatment methods include complete surgical excision and radiotherapy. Topical imiquimod and biologics are promising therapies. Here, we present a case of MCC occurring in a 76-year-old Chinese woman.

Application of Baricitinib in Dermatology.

There are four JAK subtypes: JAK1, JAK2, JAK3, and tyrosine kinase 2 (TYK2). Small molecule Janus tyrosine kinase (JAK) inhibitors can inhibit a variety of pro-inflammatory cytokines. Baricitinib is the first generation of JAK1/2 inhibitor targeting the ATPase of JAK, which blocks the intracellular transmission of cytokines through JAK-STATs. Thus far, it has been approved for the treatment of rheumatoid arthritis (RA); however, an increasing number of studies have suggested that baricitinib can be used to treat dermatological diseases, such as atopic dermatitis (AD), psoriasis, vitiligo, and alopecia areata. Baricitinib can be a new choice for the treatment of dermatological diseases, which cannot be treated with conventional drugs. We reviewed the application, efficacy, side effects, precautions, limitations and prospect of baricitinib in atopic dermatitis, psoriasis, vitiligo and alopecia areata (AA) in recent 5 years including clinical trials and case reports. Among them, the application in the field of alopecia areata is the most encouraging, and we reviewed the mechanism in detail.

3D Urchin-Like CuO Modified W18O49 Nanostructures for Promoted Photocatalytic Hydrogen Evolution under Visible Light Irradiation.

Photocatalytic hydrogen evolution is a promising" green chemistry" route driven by sunlight for the direct water splitting into value-added hydrogen energy. Herein, with the object of exploring the effect of CuO loading on W18O49 photocatalytic activity, a 3D Urchin-like CuO modified W18O49 (CuO/W18O49) microspheres with different CuO loadings were synthesized via thermochemical precipitation combined with solvent-thermal method. The obtained CuO/W18O49 microspheres were analyzed by means of X-ray diffraction (XRD), scanning electron microscope (SEM), energy-dispersive X-ray spectroscopy (EDS), transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS) and photoluminescence (PL), etc. The results infer that the urchin-like 3D morphology with a high surface area and abundant 1D nanowires promotes electron transfer, the introduction of CuO further increases the number of active sites, thereby ensuring fast interfacial charge transfer to improve photocatalytic performance. During photocatalytic H2 evolution from water splitting, 5 wt.% CuO/W18O49 shows the optimal performance, the H2 yield is almost 3.22 times that of the undoped counterparts. This work presents that oxygen-vacancy-rich heterojunction nanocomposites can be used as a new strategy to design materials with high photocatalytic activity.

Psoriasis to Psoriatic Arthritis: The Application of Proteomics Technologies.

Psoriatic disease (PsD) is a spectrum of diseases that affect both skin [cutaneous psoriasis (PsC)] and musculoskeletal features [psoriatic arthritis (PsA)]. A considerable number of patients with PsC have asymptomatic synovio-entheseal inflammations, and approximately one-third of those eventually progress to PsA with an enigmatic mechanism. Published studies have shown that early interventions to the very early-stage PsA would effectively prevent substantial bone destructions or deformities, suggesting an unmet goal for exploring early PsA biomarkers. The emergence of proteomics technologies brings a complete view of all involved proteins in PsA transitions, offers a unique chance to map all potential peptides, and allows a direct head-to-head comparison of interaction pathways in PsC and PsA. This review summarized the latest development of proteomics technologies, highlighted its application in PsA biomarker discovery, and discussed the possible clinical detectable PsA risk factors in patients with PsC.

NLK suppresses MAVS-mediated signaling in black carp antiviral innate immunity.

Mammalian Nemo-like kinase (NLK) plays important roles in multiple biological processes including immune response; however, the roles of teleost NLK remain largely unknown. In the present study, the NLK homolog (bcNLK) of black carp (Mylopharyngodon piceus) has been cloned and characterized. The coding region of bcNLK consists of 1427 nucleotides and encodes 476 amino acid, including two low complexity region (LCR) domains at the N-terminus and a serine/threonine protein kinase catalytic (S-TKc) domain in the middle region. The transcription of bcNLK are promoted after spring viremia of carp virus (SVCV) infection and poly (I:C) stimulation in host cells, but not post LPS treatment. bcNLK exhibits weak impact on the transcription of interferon (IFN) promoter in the reporter assay, however, black carp MAVS (bcMAVS)-mediated IFN promoter transcription is remarkably dampened by bcNLK. The interaction between bcNLK and bcMAVS is detected through the co-immunoprecipitation assay. Accordingly, the plaque assay results show that bcMAVS-mediated antiviral ability is impaired by bcNLK. Moreover, knockdown of bcNLK in host cells leads to the enhanced antiviral ability against SVCV. All these data support the conclusion that black carp NLK associates with MAVS and inhibited MAVS-mediated antiviral signaling.

Nociceptive Sensory Fibers Drive Interleukin-23 Production in a Murine Model of Psoriasis via Calcitonin Gene-Related Peptide.

Neuroimmunity is involved in the pathogenesis of psoriasis, but the mechanism underlying the interaction between the nervous system and the interleukin (IL)-23/IL-17 immune axis is yet unclear. This study reveals the essential role of the sensory neuron-derived calcitonin gene-related peptide (CGRP) in imiquimod (IMQ)-induced expression of IL-23. First, we show that the increased nociceptive behavior was consistent with the development of psoriasiform dermatitis, which requires intact sensory innervation. Systemic ultrapotent Transient receptor potential vanilloid 1 (TRPV1) agonist (resiniferatoxin, RTX) treatment-induced sensory denervation resulted in a significant decrease in IL-23 expression in this model, while the recombinant IL-23 treatment induced IL-17A expression was intact after RTX treatment. In addition, IMQ exposure induced a transient increase in CGRP expression in the dorsal root ganglion. The neuron-derived CGRP expression was completely abolished by sensory denervation, thereby downregulating IL-23 expression, which could be reversed through the introduction of CGRP into the denervated dorsal skin. Our results suggest that nociceptive sensory neurons may drive the production of IL-23, resulting in IL-17A production from γδ T cells via the neuropeptide CGRP in the pathology of psoriasis.

Whole-genome mate-pair sequencing of apparently balanced chromosome rearrangements reveals complex structural variations: two case studies.

BACKGROUND: Apparently balanced chromosome rearrangements (ABCRs) in non-affected individuals are well-known to possess high reproductive risks such as infertility, abnormal offspring, and pregnancy loss. However, caution should be exercised in genetic counseling and reproductive intervention because cryptic unbalanced defects and genome structural variations beyond the resolution of routine cytogenetics may not be detected. CASE PRESENTATION: Here, we studied two familial cases of ABCRs were recruited in this study. In family 1, the couple suffered two abortions pregnancies and underwent labor induction. Single nucleotide polymorphism (SNP) array analysis of the aborted sample from the second pregnancy revealed a 10.8 Mb heterozygous deletion at 10q26.13q26.3 and a 5.5 Mb duplication at 19q13.41-q13.43. The non-affected father was identified as a carrier of three-way complex chromosomal rearrangement [t (6;10;19)(p22;q26;q13)] by karyotyping. Whole-genome mate-pair sequencing revealed a cryptic breakpoint on the derivative chromosome 19 (der19), indicating that the karyotype was a more complex structural rearrangement comprising four breakpoints. Three genes, FAM24B, CACNG8, and KIAA0556, were disrupted without causing any abnormal phenotype in the carrier. In family 2, the couple suffered from a spontaneous miscarriage. This family had an affected child with multiple congenital deformities and an unbalanced karyotype, 46,XY,der (11) t (6;11)(q13;p11.2). The female partner was identified as a balanced translocation carrier with the karyotype 46,XX,t (6;11)(q13;p11.2) dn. Further SNP array and fluorescent in situ hybridization (FISH) indicated a cryptic insertion between chromosome 6 and chromosome 11. Finally, whole-genome mate-pair sequencing revealed an extremely complex genomic structural variation, including a cryptic deletion and 12 breakpoints on chromosome 11, and 1 breakpoint on chromosome 6 . CONCLUSIONS: Our study investigated two rare cases of ABCRs and demonstrated the efficacy of whole-genome mate-pair sequencing in analyzing the genome complex structural variation. In case of ABCRs detected by conventional cytogenetic techniques, whole genome sequencing (WGS) based approaches should be considered for accurate diagnosis, effective genetic counseling, and correct reproductive intervention to avoid recurrence risks.

Black carp NAP1 positively regulates MDA5-mediated antiviral signaling during the innate immune activation.

NAK-associated protein 1 (NAP1) is involved in NF-κB activation and interferon (IFN) induction in human and mammal; however, the role of teleost NAP1 in innate immunity remains unknown. In this paper, NAP1 homologue of black carp (Mylopharyngodon piceus) has been cloned and characterized. Black carp NAP1 (bcNAP1) migrated around 47 kDa in immunoblot assay and was identified as a cytosolic protein by immunofluorescent staining. bcNAP1 showed little IFN promoter-inducing ability in the reporter assay and bcNAP1 presented no antiviral activity against either grass carp reovirus (GCRV) or spring viremia of carp virus (SVCV) in the plaque assay. However, when co-expressed with black carp MDA5 (bcMDA5), bcNAP1 enhanced bcMDA5-mediated IFN promoter induction in the reporter assay. Accordingly, the plaque assay data demonstrated that the antiviral activity of bcMDA5 against both GCRV and SVCV was upregulated by bcNAP1. Additionally, the association between bcNAP1 and bcMDA5 has been identified through immunofluorescent staining and co-immunoprecipitation (co-IP) assay. Thus, the data generated in this study support the conclusion that bcNAP1 interacts with bcMDA5 and up-regulates bcMDA5-mediated antiviral signaling during host innate immune activation.

Black carp RIPK1 negatively regulates MAVS-mediated antiviral signaling during the innate immune activation.

Receptor-interacting serine/threonine protein kinase 1 (RIPK1) is an important regulator of necroptosis and involved in innate immune response in human and mammal; however, its function in teleost fish mains largely unknown. In this paper, the RIPK1 homologue of black carp (Mylopharyngodon piceus) has been cloned and characterized to explore its role in immunity. Black carp RIPK1 (bcRIPK1) possesses the similar structure to its mammalian counterpart, which has been identified as a cytosolic protein by immunofluorescence staining. Overexpressed bcRIPK1 in host cells led to the decreased transcription of interferon (IFN) and interferon stimulated genes, and exogenous bcRIPK1 in EPC cells led to the decreased transcription of interferon promoters in reporter assay. Our previous study has identified that black carp MAVS (bcMAVS) functions as an antiviral adaptor protein against both grass carp reovirus (GCRV) and spring viremia of carp virus (SVCV). The reporter assay showed that the IFN-inducing ability of bcMAVS was dampened by bcRIPK1 and the plaque assay demonstrated that the antiviral activity of bcMAVS was inhibited by bcRIPK1. The immunofluorescent staining and co-immunoprecipitation identified the interaction between these two molecules. Thus, the data generated in this paper support the conclusion that bcRIPK1 interacts with bcMAVS and negatively regulates bcMAVS-mediated antiviral signaling.

Hemophagocytic lymphohistiocytosis presenting with annular erythema multiforme-like eruptions in a patient with angioimmunoblastic T cell lymphoma: A case report.

Angioimmunoblastic T cell lymphoma (AITL)-associated hemophagocytic lymphohistiocytosis (HLH) rarely occurs with annular erythema multiforme-like rashes. The present case report describes a patient who was misdiagnosed with erythema multiforme at an early stage of the disease due to annular erythema multiforme-like eruptions. However, antihistamine treatment was ineffective. The patient progressed rapidly with high fever, hepatosplenomegaly and pharyngitis. The number of copies of Epstein-Barr virus DNA continuously increased. Accompanied by the swelling of lymph nodes, the blood cell count decreased. Further bone-marrow examination and biopsy of the lymph nodes were conducted. The patient was eventually diagnosed with AITL-associated HLH, and treated with etoposide together with cyclophosphamide, doxorubicin, vincristine and prednisolone. The patient was successfully treated with several courses of chemotherapy. In view of the fact that AITL-associated HLH with annular erythema multiforme-like rashes is relatively rare worldwide and is associated with a high mortality rate, the data on previous cases were reviewed with the hope of providing clinical bases for early diagnosis and treatment of AITL-associated HLH.

C19, a C-terminal peptide of CKLF1, decreases inflammation and proliferation of dermal capillaries in psoriasis.

Psoriasis is a chronic inflammatory autoimmune disease with undefined etiology. Chemokine-like factor 1 (CKLF1), a human cytokine that is a functional ligand for CCR4, displays chemotactic activities in a wide spectrum of leukocytes and plays an important role in psoriasis development. In previous study, our laboratory found that the expression of CKLF1 increased in psoriatic lesions. C19 as a CKLF1's C-terminal peptide has been reported to exert inhibitory effects on a variety of diseases. However, the protective roles of C19 in endothelial cells proliferation and inflammatory cells chemotaxis remain elusive in psoriasis. In this study we examined the protective effect of C19 on both the cellular model and the animal model. The effects of C19 on endothelial cells proliferation and inflammatory cells chemotaxis were investigated in cultured human umbilical vein endothelial cells (HUVECs) and imiquimod-induced psoriasiform inflammation of BALB/c mice based on techniques including immunohistochemical analysis, quantitative real-time PCR (qRT-PCR), western blot, transwell, and EdU assay. This study shows that CKLF1-C19 significantly protects against psoriasis by inhibiting the infiltration of inflammatory cells and proliferation of microvascular cells, possibly via inhibiting MAPK pathways.