{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T14:13:41Z","timestamp":1776867221945,"version":"3.51.2"},"reference-count":93,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,15]],"date-time":"2023-02-15T00:00:00Z","timestamp":1676419200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CIHR MOP","award":["142257"],"award-info":[{"award-number":["142257"]}]},{"name":"Canadian Dermatology Foundation","award":["142257"],"award-info":[{"award-number":["142257"]}]},{"name":"Innovaderm Research","award":["142257"],"award-info":[{"award-number":["142257"]}]},{"name":"Department of Medicine, McGill","award":["142257"],"award-info":[{"award-number":["142257"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Atopic dermatitis (AD) is known as a skin disease; however, T cell immunopathology found in blood is associated with its severity. Skin Staphylococcus aureus (S. aureus) and associated host\u2013pathogen dynamics are important to chronic T helper 2 (Th2)-dominated inflammation in AD, yet they remain poorly understood. This study sought to investigate the effects of S. aureus-derived molecules and skin alarmins on human peripheral blood mononuclear cells, specifically testing Th2-type cells, cytokines, and chemokines known to be associated with AD. We first show that six significantly elevated Th2-related chemokine biomarkers distinguish blood from adult AD patients compared to healthy controls ex vivo; in addition, TARC\/CCL17, LDH, and PDGF-AA\/AB correlated significantly with disease severity. We then demonstrate that these robust AD-associated biomarkers, as well as associated type 2 T cell functions, are readily reproduced from healthy blood mononuclear cells exposed to the alarmin TSLP and the S. aureus superantigen SEB in a human in vitro model, including IL-13, IL-5, and TARC secretion as well as OX-40-expressing activated memory T cells. We further show that the agonism of nucleotide-binding oligomerization domain-containing protein (NOD)2 inhibits this IL-13 secretion and memory Th2 and Tc2 cell functional activation while inducing significantly increased pSTAT3 and IL-6, both critical for Th17 cell responses. These findings identify NOD2 as a potential regulator of type 2 immune responses in humans and highlight its role as an endogenous inhibitor of pathogenic IL-13 that may open avenues for its therapeutic targeting in AD.<\/jats:p>","DOI":"10.3390\/biom13020369","type":"journal-article","created":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T02:04:03Z","timestamp":1676513043000},"page":"369","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["NOD2 Agonism Counter-Regulates Human Type 2 T Cell Functions in Peripheral Blood Mononuclear Cell Cultures: Implications for Atopic Dermatitis"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5055-208X","authenticated-orcid":false,"given":"Vladimir-Andrey","family":"Gimenez-Rivera","sequence":"first","affiliation":[{"name":"Infectious Diseases and Immunity in Global Health, Center for Translational Biology, The Research Institute of the McGill University Health Center, Montr\u00e9al, QC H4A 3J1, Canada"},{"name":"Division of Experimental Medicine, Department of Medicine, McGill University, Montr\u00e9al, QC H4A 3J1, Canada"},{"name":"IntegraSkin GmbH, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harshita","family":"Patel","sequence":"additional","affiliation":[{"name":"Infectious Diseases and Immunity in Global Health, Center for Translational Biology, The Research Institute of the McGill University Health Center, Montr\u00e9al, QC H4A 3J1, Canada"},{"name":"Division of Experimental Medicine, Department of Medicine, McGill University, Montr\u00e9al, QC H4A 3J1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Franck P.","family":"Dupuy","sequence":"additional","affiliation":[{"name":"Infectious Diseases and Immunity in Global Health, Center for Translational Biology, The Research Institute of the McGill University Health Center, Montr\u00e9al, QC H4A 3J1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5194-2792","authenticated-orcid":false,"given":"Zoulfia","family":"Allakhverdi","sequence":"additional","affiliation":[{"name":"Infectious Diseases and Immunity in Global Health, Center for Translational Biology, The Research Institute of the McGill University Health Center, Montr\u00e9al, QC H4A 3J1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2430-0035","authenticated-orcid":false,"given":"Charlie","family":"Bouchard","sequence":"additional","affiliation":[{"name":"Infectious Diseases and Immunity in Global Health, Center for Translational Biology, The Research Institute of the McGill University Health Center, Montr\u00e9al, QC H4A 3J1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joaqu\u00edn","family":"Madrenas","sequence":"additional","affiliation":[{"name":"Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Bissonnette","sequence":"additional","affiliation":[{"name":"Innovaderm Research, Montr\u00e9al, QC H2X 2V1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ciriaco A.","family":"Piccirillo","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, McGill University, Montr\u00e9al, QC H3A 2B4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0376-3324","authenticated-orcid":false,"given":"Carolyn","family":"Jack","sequence":"additional","affiliation":[{"name":"Infectious Diseases and Immunity in Global Health, Center for Translational Biology, The Research Institute of the McGill University Health Center, Montr\u00e9al, QC H4A 3J1, Canada"},{"name":"Division of Experimental Medicine, Department of Medicine, McGill University, Montr\u00e9al, QC H4A 3J1, Canada"},{"name":"Department of Microbiology and Immunology, McGill University, Montr\u00e9al, QC H3A 2B4, Canada"},{"name":"Division of Dermatology, Department of Medicine, McGill University, Montr\u00e9al, QC H4A 3J1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1038\/jid.2013.446","article-title":"The Global Burden of Skin Disease in 2010: An Analysis of the Prevalence and Impact of Skin Conditions","volume":"134","author":"Hay","year":"2014","journal-title":"J. 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