{"doi":"10.1016/j.jid.2023.09.281","title":"Psoriatic Neutrophils Are Primed in Circulation for Enhanced β2-Integrin–Dependent Recruitment and Effector Function on E-Selectin and ICAM-1","abstract":"Psoriasis is an inflammatory disease that is initiated by pathogenic T cells within skin lesions that correlates with hyperproliferation of keratinocytes and the release of cytokines and damage-associated molecular pattern molecules into the circulation (Wang and Jin, 2020Wang W.M. Jin H.Z. Role of neutrophils in psoriasis.J Immunol Res. 2020; 20203709749Crossref Scopus (39) Google Scholar). Exposure to damage-associated molecular patterns and low levels of cytokines and chemokines shift neutrophils from a quiescent to a primed state characterized by increased sensitivity to subsequent stimulation that induces amplified adhesive and effector function at sites of tissue inflammation (Miralda et al., 2017Miralda I. Uriarte S.M. McLeish K.R. Multiple phenotypic changes define neutrophil priming.Front Cell Infect Microbiol. 2017; 7: 217Crossref PubMed Scopus (125) Google Scholar). An early event in psoriatic plaque formation is the recruitment of primed neutrophils into the dermis where they degranulate, release ROS, and produce neutrophil extracellular traps enriched in damage-associated molecular patterns, which include cathelicidin (LL37) and calprotectin (S100A8/A9) that exacerbate skin inflammation (Shao et al., 2019Shao S. Fang H. Dang E. Xue K. Zhang J. Li B. et al.Neutrophil extracellular traps promote inflammatory responses in psoriasis via activating epidermal TLR4/IL-36R crosstalk.Front Immunol. 2019; 10: 746Crossref PubMed Scopus (108) Google Scholar). In particular, calprotectin levels rise with neutrophil count in circulation, which correlates with the intensity of plaque formation in psoriasis and cardiovascular disease comorbidity (Berg et al., 2022Berg A.R. Hong C.G. Svirydava M. Li H. Parel P.M. Florida E. et al.Association of S100A8/A9 with lipid-rich necrotic core and treatment with biologic therapy in patients with psoriasis: results from an observational cohort study.J Invest Dermatol. 2022; 142: 2909-2919Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar; Matsunaga et al., 2021Matsunaga Y. Hashimoto Y. Ishiko A. Stratum corneum levels of calprotectin proteins S100A8/A9 correlate with disease activity in psoriasis patients.J Dermatol. 2021; 48: 1518-1525Crossref PubMed Scopus (13) Google Scholar). Calprotectin signals through toll-like receptor 4 to elicit an allosteric upshift of β2-integrins (CD11/CD18) from a bent to extended conformation with intermediate affinity to bind ICAM-1 on inflamed endothelium (Pruenster et al., 2015Pruenster M. Kurz A.R. Chung K.J. Cao-Ehlker X. Bieber S. Nussbaum C.F. et al.Extracellular MRP8/14 is a regulator of β2 integrin-dependent neutrophil slow rolling and adhesion.Nat Commun. 2015; 6: 6915Crossref PubMed Scopus (130) Google Scholar). Previously, we reported that ligation of L-selectin on neutrophils rolling on E-selectin elicits the secretion of calprotectin that primes them for enhanced recruitment efficiency on inflamed endothelium (Morikis et al., 2017Morikis V.A. Chase S. Wun T. Chaikof E.L. Magnani J.L. Simon S.I. Selectin catch-bonds mechanotransduce integrin activation and neutrophil arrest on inflamed endothelium under shear flow.Blood. 2017; 130: 2101-2110Crossref PubMed Scopus (62) Google Scholar). In this study, we examined the importance of calprotectin in priming for enhanced β2-integrin–mediated neutrophil inflammatory response in psoriasis. Fresh venous blood from patients with psoriasis and healthy subjects were collected after written informed consent, and studies were approved by the University of California, Davis Institutional Review Board Clinical Committee B (Supplementary Table S1). Neutrophil priming through toll-like receptor 4 signaling elicits degranulation that induces upregulation of Mac-1 (CD11b/CD18) and shedding of L-selectin (CD62L). Psoriatic neutrophils in diluted whole blood exhibited a primed phenotype, with Mac-1 upregulated by 150% and L-selectin decreased by 25% relative to that in healthy subjects (Supplementary Fig","journal":"Journal of Investigative Dermatology","year":2023,"id":373661,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9425,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1134950,"name":"Szu Jung Chen","orcid":"0009-0003-2267-3759","position":1,"is_corresponding":false},{"id":1134951,"name":"Megan R. Westerland","orcid":"0009-0002-2869-4289","position":2,"is_corresponding":false},{"id":656578,"name":"Xuesong Wu","orcid":"0000-0003-0093-6338","position":3,"is_corresponding":false},{"id":626483,"name":"Samuel Hwang","orcid":"0000-0001-7930-9964","position":4,"is_corresponding":false},{"id":482436,"name":"Scott I. Simon","orcid":"0000-0003-1186-6611","position":5,"is_corresponding":false},{"id":504610,"name":"Gustavo Garcia","orcid":"0000-0003-1691-4571","position":0,"is_corresponding":true}],"reference_count":12,"raw_metadata":null,"created_at":"2026-07-19T01:16:07.080027Z","pmid":"37879398","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}