{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T22:44:23Z","timestamp":1784241863815,"version":"3.55.0"},"reference-count":84,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T00:00:00Z","timestamp":1690416000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100002590","name":"American Lung Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002590","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008333","name":"University of Alabama at Birmingham","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008333","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008333","name":"University of Alabama at Birmingham","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008333","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Data from patient cohorts and mouse models of atopic dermatitis, food allergy and asthma strongly support a role for chitinase-3-like-1 protein (CHI3L1) in allergic disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To address whether Chi3l1 also contributes to T<jats:sub>H<\/jats:sub>2 responses following nematode infection, we infected <jats:italic>Chi3l1<\/jats:italic><jats:sup>-\/-<\/jats:sup> mice with <jats:italic>Heligmosomoides polygyrus<\/jats:italic> (<jats:italic>Hp<\/jats:italic>) and analyzed T cell responses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>As anticipated, we observed impaired T<jats:sub>H<\/jats:sub>2 responses in <jats:italic>Hp<\/jats:italic>-infected <jats:italic>Chi3l1<\/jats:italic><jats:sup>-\/-<\/jats:sup> mice. However, we also found that T cell intrinsic expression of <jats:italic>Chi3l1<\/jats:italic> was required for ICOS upregulation following activation of na\u00efve CD4 T cells and was necessary for the development of the IL-4<jats:sup>+<\/jats:sup> T<jats:sub>FH<\/jats:sub> subset, which supports germinal center B cell reactions and IgE responses. We also observed roles for <jats:italic>Chi3l1<\/jats:italic> in T<jats:sub>FH<\/jats:sub>, germinal center B cell, and IgE responses to alum-adjuvanted vaccination. While <jats:italic>Chi3l1<\/jats:italic> was critical for IgE humoral responses it was not required for vaccine or infection-induced IgG1 responses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>These results suggest that <jats:italic>Chi3l1<\/jats:italic> modulates IgE responses, which are known to be highly dependent on IL-4-producing T<jats:sub>FH<\/jats:sub> cells.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1158493","type":"journal-article","created":{"date-parts":[[2023,7,28]],"date-time":"2023-07-28T01:04:46Z","timestamp":1690506286000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Chitinase-3-like 1 regulates TH2 cells, TFH cells and IgE responses to helminth infection"],"prefix":"10.3389","volume":"14","author":[{"given":"Miranda L.","family":"Curtiss","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander F.","family":"Rosenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher D.","family":"Scharer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betty","family":"Mousseau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia A. Ballesteros","family":"Benavides","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John E.","family":"Bradley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Le\u00f3n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chad","family":"Steele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Troy D.","family":"Randall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances E.","family":"Lund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,7,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3389\/falgy.2022.818732","article-title":"The effector function of allergens","volume":"3","author":"Hazebrouck","year":"2022","journal-title":"Front Allergy"},{"key":"B2","doi-asserted-by":"publisher","first-page":"903659","DOI":"10.1155\/2012\/903659","article-title":"Role of allergen source-derived proteases in sensitization via airway epithelial cells","volume":"2012","author":"Matsumura","year":"2012","journal-title":"J Allergy (Cairo)"},{"key":"B3","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1080\/10408690390826455","article-title":"Chitin\u2013the undisputed biomolecule of great potential","volume":"43","author":"Tharanathan","year":"2003","journal-title":"Crit Rev Food Sci Nutr"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2005.03.011","article-title":"Parasitic nematodes have two distinct chitin synthases","volume":"142","author":"Foster","year":"2005","journal-title":"Mol Biochem Parasitol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200912-1877OC","article-title":"Chitin particles are multifaceted immune adjuvants","volume":"182","author":"Da Silva","year":"2010","journal-title":"Am J Respir Crit Care Med"},{"key":"B6","doi-asserted-by":"publisher","first-page":"11721","DOI":"10.1038\/s41598-018-30259-2","article-title":"Chitin promotes antigen-specific Th2 cell-mediated murine asthma through induction of IL-33-mediated IL-1beta production by DCs","volume":"8","author":"Arae","year":"2018","journal-title":"Sci Rep"},{"key":"B7","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1146\/annurev-physiol-012110-142250","article-title":"Role of chitin and chitinase\/chitinase-like proteins in inflammation, tissue remodeling, and injury","volume":"73","author":"Lee","year":"2011","journal-title":"Annu Rev Physiol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20081271","article-title":"Role of breast regression protein 39 (BRP-39)\/chitinase 3-like-1 in Th2 and IL-13-induced tissue responses and apoptosis","volume":"206","author":"Lee","year":"2009","journal-title":"J Exp Med"},{"key":"B9","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1186\/1465-9921-12-39","article-title":"Differential expression and function of breast regression protein 39 (BRP-39) in murine models of subacute cigarette smoke exposure and allergic airway inflammation","volume":"12","author":"Nikota","year":"2011","journal-title":"Respir Res"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1507393112","article-title":"AMCase is a crucial regulator of type 2 immune responses to inhaled house dust mites","volume":"112","author":"Kim","year":"2015","journal-title":"Proc Natl Acad Sci U.S.A."},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1111\/all.13426","article-title":"Chitotriosidase inhibits allergic asthmatic airways via regulation of TGF-beta expression and Foxp3(+) Treg cells","volume":"73","author":"Hong","year":"2018","journal-title":"Allergy"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aba9337","article-title":"Natural polymorphism of Ym1 regulates pneumonitis through alternative activation of macrophages","volume":"6","author":"Zhu","year":"2020","journal-title":"Sci Adv"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa073600","article-title":"A chitinase-like protein in the lung and circulation of patients with severe asthma","volume":"357","author":"Chupp","year":"2007","journal-title":"N Engl J Med"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0708801","article-title":"Effect of variation in CHI3L1 on serum YKL-40 level, risk of asthma, and lung function","volume":"358","author":"Ober","year":"2008","journal-title":"N Engl J Med"},{"key":"B15","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.jaci.2014.11.027","article-title":"Genetic variation in chitinase 3-like 1 (CHI3L1) contributes to asthma severity and airway expression of YKL-40","volume":"136","author":"Gomez","year":"2015","journal-title":"J Allergy Clin Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00800-2017","article-title":"Characterisation of asthma subgroups associated with circulating YKL-40 levels","volume":"4","author":"Gomez","year":"2017","journal-title":"Eur Respir J"},{"key":"B17","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1186\/s12931-019-1051-9","article-title":"Chitinase-like protein YKL-40 correlates with inflammatory phenotypes, anti-asthma responsiveness and future exacerbations","volume":"20","author":"Liu","year":"2019","journal-title":"Respir Res"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200809-1422OC","article-title":"Genetic variation in the promoter region of chitinase 3-like 1 is associated with atopy","volume":"179","author":"Sohn","year":"2009","journal-title":"Am J Respir Crit Care Med"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2011.02596.x","article-title":"Serum YKL-40 levels are correlated with symptom severity in patients with allergic rhinitis","volume":"66","author":"Kwon","year":"2011","journal-title":"Allergy"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0167453","article-title":"Genetic variants in CHIA and CHI3L1 are associated with the IgE response to the ascaris resistance marker ABA-1 and the birch pollen allergen bet v 1","volume":"11","author":"Acevedo","year":"2016","journal-title":"PloS One"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1111\/iji.12327","article-title":"SPINK5 is associated with early-onset and CHI3L1 with late-onset atopic dermatitis","volume":"44","author":"Dezman","year":"2017","journal-title":"Int J Immunogenet"},{"key":"B22","doi-asserted-by":"publisher","first-page":"5746031","DOI":"10.1155\/2017\/5746031","article-title":"Chitinase-3-like protein 1 (YKL-40) reflects the severity of symptoms in atopic dermatitis","volume":"2017","author":"Salomon","year":"2017","journal-title":"J Immunol Res"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1111\/cea.13478","article-title":"Chitinase 3-like 1 drives allergic skin inflammation via Th2 immunity and M2 macrophage activation","volume":"49","author":"Kwak","year":"2019","journal-title":"Clin Exp Allergy"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.4168\/aair.2020.12.6.1012","article-title":"Chitinase 3-like 1 contributes to food allergy via M2 macrophage polarization","volume":"12","author":"Kim","year":"2020","journal-title":"Allergy Asthma Immunol Res"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00528.2020","article-title":"Chitinase 3-like-1 protects airway function despite promoting type 2 inflammation during fungal-associated allergic airway inflammation","volume":"320","author":"Mackel","year":"2021","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.739","article-title":"New therapeutic strategy for atopic dermatitis by targeting CHI3L1\/ITGA5 axis","volume":"12","author":"Lee","year":"2022","journal-title":"Clin Transl Med"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/nri2992","article-title":"Diversity and dialogue in immunity to helminths","volume":"11","author":"Allen","year":"2011","journal-title":"Nat Rev Immunol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/484458a","article-title":"Forum: immunology: allergy challenged","volume":"484","author":"Artis","year":"2012","journal-title":"Nature"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-012-0347-3","article-title":"Immunity to the model intestinal helminth parasite Heligmosomoides polygyrus","volume":"34","author":"Reynolds","year":"2012","journal-title":"Semin Immunopathol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00061","article-title":"Helminth allergens, parasite-specific IgE, and its protective role in human immunity","volume":"5","author":"Fitzsimmons","year":"2014","journal-title":"Front Immunol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3023","article-title":"Chitinase-like proteins promote IL-17-mediated neutrophilia in a tradeoff between nematode killing and host damage","volume":"15","author":"Sutherland","year":"2014","journal-title":"Nat Immunol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4894(91)90074-7","article-title":"Heligmosomoides polygyrus: CD4+ but not CD8+ T cells regulate the IgE response and protective immunity in mice","volume":"73","author":"Urban","year":"1991","journal-title":"Exp Parasitol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20090313","article-title":"IL-4-producing CD4+ T cells in reactive lymph nodes during helminth infection are T follicular helper cells","volume":"206","author":"King","year":"2009","journal-title":"J Exp Med"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2309","article-title":"Regulation of T(H)2 development by CXCR5+ dendritic cells and lymphotoxin-expressing B cells","volume":"13","author":"Leon","year":"2012","journal-title":"Nat Immunol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1700141","article-title":"T follicular helper cell-derived IL-4 is required for IgE production during intestinal helminth infection","volume":"199","author":"Meli","year":"2017","journal-title":"J Immunol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaw6433","article-title":"Identification of a T follicular helper cell subset that drives anaphylactic IgE","volume":"365","author":"Gowthaman","year":"2019","journal-title":"Science."},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2008.08.014","article-title":"Polyclonal and specific antibodies mediate protective immunity against enteric helminth infection","volume":"4","author":"McCoy","year":"2008","journal-title":"Cell Host Microbe"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.4.2340","article-title":"The role of ICOS in the CXCR5+ follicular B helper T cell maintenance in vivo","volume":"175","author":"Akiba","year":"2005","journal-title":"J Immunol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.03.023","article-title":"ICOS receptor instructs T follicular helper cell versus effector cell differentiation via induction of the transcriptional repressor Bcl6","volume":"34","author":"Choi","year":"2011","journal-title":"Immunity"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3554","article-title":"TFH cells progressively differentiate to regulate the germinal center response","volume":"17","author":"Weinstein","year":"2016","journal-title":"Nat Immunol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aaw7636","article-title":"Inhibition of IL-2 responsiveness by IL-6 is required for the generation of GC-TFH cells","volume":"4","author":"Papillion","year":"2019","journal-title":"Sci Immunol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/nature07444","article-title":"X-ray structure of NS1 from a highly pathogenic H5N1 influenza virus","volume":"456","author":"Bornholdt","year":"2008","journal-title":"Nature"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.01.006","article-title":"Cytokine-producing effector B cells regulate type 2 immunity to H. polygyrus","volume":"30","author":"Wojciechowski","year":"2009","journal-title":"Immunity"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.03.014","article-title":"Omental milky spots develop in the absence of lymphoid tissue-inducer cells and support B and T cell responses to peritoneal antigens","volume":"30","author":"Rangel-Moreno","year":"2009","journal-title":"Immunity"},{"key":"B45","doi-asserted-by":"publisher","first-page":"1172","DOI":"10.1016\/j.immuni.2019.04.004","article-title":"T-bet transcription factor promotes antibody-secreting cell differentiation by limiting the inflammatory effects of IFN-gamma on B cells","volume":"50","author":"Stone","year":"2019","journal-title":"Immunity"},{"key":"B46","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1186\/1471-2105-15-182","article-title":"Skewer: a fast and accurate adapter trimmer for next-generation sequencing paired-end reads","volume":"15","author":"Jiang","year":"2014","journal-title":"BMC Bioinf"},{"key":"B47","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1003118","article-title":"Software for computing and annotating genomic ranges","volume":"9","author":"Lawrence","year":"2013","journal-title":"PloS Comput Biol"},{"key":"B49","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc Natl Acad Sci U.S.A."},{"key":"B51","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1038\/s41467-017-02731-6","article-title":"Regulation of chitinase-3-like-1 in T cell elicits Th1 and cytotoxic responses to inhibit lung metastasis","volume":"9","author":"Kim","year":"2018","journal-title":"Nat Commun"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.150.8.3434","article-title":"A primary intestinal helminthic infection rapidly induces a gut-associated elevation of Th2-associated cytokines and IL-3","volume":"150","author":"Svetic","year":"1993","journal-title":"J Immunol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20090303","article-title":"T follicular helper cells differentiate from Th2 cells in response to helminth antigens","volume":"206","author":"Glatman Zaretsky","year":"2009","journal-title":"J Exp Med"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1126\/science.1175870","article-title":"Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation","volume":"325","author":"Johnston","year":"2009","journal-title":"Science"},{"key":"B55","doi-asserted-by":"publisher","first-page":"190","DOI":"10.4049\/jimmunol.0903505","article-title":"Germinal center T follicular helper cell IL-4 production is dependent on signaling lymphocytic activation molecule receptor (CD150)","volume":"185","author":"Yusuf","year":"2010","journal-title":"J Immunol"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1126\/science.1176676","article-title":"Bcl6 mediates the development of T follicular helper cells","volume":"325","author":"Nurieva","year":"2009","journal-title":"Science"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.07.002","article-title":"The transcriptional repressor Bcl-6 directs T follicular helper cell lineage commitment","volume":"31","author":"Yu","year":"2009","journal-title":"Immunity"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1837","article-title":"Effectors and memories: Bcl-6 and Blimp-1 in T and B lymphocyte differentiation","volume":"11","author":"Crotty","year":"2010","journal-title":"Nat Immunol"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201242794","article-title":"ICOS controls Foxp3(+) regulatory T-cell expansion, maintenance and IL-10 production during helminth infection","volume":"43","author":"Redpath","year":"2013","journal-title":"Eur J Immunol"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20042572","article-title":"Suppression of allergic airway inflammation by helminth-induced regulatory T cells","volume":"202","author":"Wilson","year":"2005","journal-title":"J Exp Med"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200939644","article-title":"Establishment of nematode infection despite increased Th2 responses and immunopathology after selective depletion of Foxp3+ cells","volume":"39","author":"Rausch","year":"2009","journal-title":"Eur J Immunol"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.5650070506","article-title":"Identification of proteins secreted by human osteoblastic cells in culture","volume":"7","author":"Johansen","year":"1992","journal-title":"J Bone Miner Res"},{"key":"B63","first-page":"172","article-title":"Studies on serum YKL-40 as a biomarker in diseases with inflammation, tissue remodelling, fibroses and cancer","volume":"53","author":"Johansen","year":"2006","journal-title":"Dan Med Bull"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1667\/0033-7587(2000)153[0587:AEOWBP]2.0.CO;2","article-title":"Acute effects of whole-body proton irradiation on the immune system of the mouse","volume":"153","author":"Eric","year":"2000","journal-title":"Radiat Res"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2014.04.009","article-title":"Radiation sensitivity of human and murine peripheral blood lymphocytes, stem and progenitor cells","volume":"1846","author":"Heylmann","year":"2014","journal-title":"Biochim Biophys Acta"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.1RI0121-066R","article-title":"A review of signaling and transcriptional control in T follicular helper cell differentiation","volume":"111","author":"Hart","year":"2022","journal-title":"J Leukoc Biol"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2016.127","article-title":"Intestinal helminth infection impacts the systemic distribution and function of the naive lymphocyte pool","volume":"10","author":"King","year":"2017","journal-title":"Mucosal Immunol"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1601434","article-title":"IL-4 haploinsufficiency specifically impairs IgE responses against allergens in mice","volume":"198","author":"Robinson","year":"2017","journal-title":"J Immunol"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1500497","article-title":"Nonredundant roles of IL-21 and IL-4 in the phased initiation of germinal center B cells and subsequent self-renewal transitions","volume":"201","author":"Gonzalez","year":"2018","journal-title":"J Immunol"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1715","article-title":"Cytokine-secreting follicular T cells shape the antibody repertoire","volume":"10","author":"Reinhardt","year":"2009","journal-title":"Nat Immunol"},{"key":"B71","doi-asserted-by":"publisher","first-page":"43273","DOI":"10.1038\/srep43273","article-title":"Drosophila imaginal disc growth factor 2 is a trophic factor involved in energy balance, detoxification, and innate immunity","volume":"7","author":"Broz","year":"2017","journal-title":"Sci Rep"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.221458698","article-title":"Genome-wide analysis of the Drosophila immune response by using oligonucleotide microarrays","volume":"98","author":"De Gregorio","year":"2001","journal-title":"Proc Natl Acad Sci U.S.A."},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2004.03.150","article-title":"The instantly released Drosophila immune proteome is infection-specific","volume":"317","author":"Vierstraete","year":"2004","journal-title":"Biochem Biophys Res Commun"},{"key":"B74","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1159\/000353734","article-title":"Genome-wide transcriptional analysis of Drosophila larvae infected by entomopathogenic nematodes shows involvement of complement, recognition and extracellular matrix proteins","volume":"6","author":"Arefin","year":"2014","journal-title":"J Innate Immun"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.2.1279","article-title":"Identification of a novel eosinophil chemotactic cytokine (ECF-L) as a chitinase family protein","volume":"275","author":"Owhashi","year":"2000","journal-title":"J Biol Chem"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M303371200","article-title":"Structure and ligand-induced conformational change of the 39-kDa glycoprotein from human articular chondrocytes","volume":"278","author":"Houston","year":"2003","journal-title":"J Biol Chem"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.9.5035","article-title":"Mouse inducible costimulatory molecule (ICOS) expression is enhanced by CD28 costimulation and regulates differentiation of CD4+ T cells","volume":"165","author":"McAdam","year":"2000","journal-title":"J Immunol"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M604081200","article-title":"Regulation of mouse inducible costimulator (ICOS) expression by Fyn-NFATc2 and ERK signaling in T cells","volume":"281","author":"Tan","year":"2006","journal-title":"J Biol Chem"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.7150\/thno.65522","article-title":"Targeting protumor factor chitinase-3-like-1 secreted by Rab37 vesicles for cancer immunotherapy","volume":"12","author":"Yang","year":"2022","journal-title":"Theranostics"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-020-0781-7","article-title":"Strength of tonic T cell receptor signaling instructs T follicular helper cell-fate decisions","volume":"21","author":"Bartleson","year":"2020","journal-title":"Nat Immunol"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1038\/nature13803","article-title":"T-B-cell entanglement and ICOSL-driven feed-forward regulation of germinal centre reaction","volume":"517","author":"Liu","year":"2015","journal-title":"Nature"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1111\/all.13602","article-title":"Targeting the ICOS\/ICOS-L pathway in a mouse model of established allergic asthma disrupts T follicular helper cell responses and ameliorates disease","volume":"74","author":"Uwadiae","year":"2019","journal-title":"Allergy"},{"key":"B83","doi-asserted-by":"publisher","first-page":"108394","DOI":"10.1016\/j.intimp.2021.108394","article-title":"The role of ICOS in allergic disease: Positive or Negative","volume":"103","author":"Zhang","year":"2022","journal-title":"Int Immunopharmacol"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20190472","article-title":"IL-21 is a broad negative regulator of IgE class switch recombination in mouse and human B cells","volume":"217","author":"Yang","year":"2020","journal-title":"J Exp Med"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1158493\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,28]],"date-time":"2023-07-28T01:04:57Z","timestamp":1690506297000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1158493\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,27]]},"references-count":84,"alternative-id":["10.3389\/fimmu.2023.1158493"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2023.1158493","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,27]]},"article-number":"1158493"}}