{"doi":"10.4049/jimmunol.170.3.1150","title":"Deregulated MHC Class II Transactivator Expression Leads to a Strong Th2 Bias in CD4+ T Lymphocytes","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>The MHC class II (MHC-II) transactivator (CIITA) is the master transcriptional regulator of genes involved in MHC-II-restricted Ag presentation. Fine tuning of CIITA gene expression determines the cell type-specific expression of MHC-II genes. This regulation is achieved by the selective usage of multiple CIITA promoters. It has recently been suggested that CIITA also contributes to Th cell differentiation by suppressing IL-4 expression in Th1 cells. In this study, we show that endogenous CIITA is expressed at low levels in activated mouse T cells. Importantly CIITA is not regulated differentially in murine and human Th1 and Th2 cells. Ectopic expression of a CIITA transgene in multiple mouse cell types including T cells, does not interfere with normal development of CD4+ T cells. However, upon TCR activation the CIITA transgenic CD4+ T cells preferentially differentiate into IL-4-secreting Th2-type cells. These results imply that CIITA is not a direct Th1-specific repressor of the IL-4 gene and that tight control over the expression of CIITA and MHC-II is required to maintain the normal balance between Th1 and Th2 responses.</jats:p>","journal":"The Journal of Immunology","year":2003,"id":655388,"datarank":0.5416376868966337,"base_score":3.6109179126442243,"endowment":3.6109179126442243,"self_citation_contribution":0.5416376868966337,"citation_network_contribution":0.0,"self_endowment_contribution":0.5416376868966337,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":36,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1710835,"name":"Fabienne Tacchini-Cottier","orcid":null,"position":1,"is_corresponding":false},{"id":240216,"name":"Michael Lohoff","orcid":"0000-0002-5204-4289","position":2,"is_corresponding":false},{"id":399213,"name":"Francesco Annunziato","orcid":"0000-0001-8798-7589","position":3,"is_corresponding":false},{"id":111485,"name":"Lorenzo Cosmi","orcid":null,"position":4,"is_corresponding":false},{"id":1710836,"name":"Leonardo Scarpellino","orcid":null,"position":5,"is_corresponding":false},{"id":1710837,"name":"Jacques Louis","orcid":null,"position":6,"is_corresponding":false},{"id":1710838,"name":"Viktor Steimle","orcid":null,"position":7,"is_corresponding":false},{"id":1531856,"name":"Walter Reith","orcid":null,"position":8,"is_corresponding":false},{"id":1710839,"name":"Hans Acha-Orbea","orcid":null,"position":9,"is_corresponding":false},{"id":1710834,"name":"Luc A Otten","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Deregulated MHC Class II Transactivator Expression Leads to a Strong Th2 Bias in CD4+ T Lymphocytes","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>The MHC class II (MHC-II) transactivator (CIITA) is the master transcriptional regulator of genes involved in MHC-II-restricted Ag presentation. Fine tuning of CIITA gene expression determines the cell type-specific expression of MHC-II genes. This regulation is achieved by the selective usage of multiple CIITA promoters. It has recently been suggested that CIITA also contributes to Th cell differentiation by suppressing IL-4 expression in Th1 cells. In this study, we show that endogenous CIITA is expressed at low levels in activated mouse T cells. Importantly CIITA is not regulated differentially in murine and human Th1 and Th2 cells. Ectopic expression of a CIITA transgene in multiple mouse cell types including T cells, does not interfere with normal development of CD4+ T cells. However, upon TCR activation the CIITA transgenic CD4+ T cells preferentially differentiate into IL-4-secreting Th2-type cells. These results imply that CIITA is not a direct Th1-specific repressor of the IL-4 gene and that tight control over the expression of CIITA and MHC-II is required to maintain the normal balance between Th1 and Th2 responses.</jats:p>","is_dataset_classified":null,"base_score":3.6109179126442243,"endowment":3.6109179126442243,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"12538670","pmcid":null,"openalex_id":"https://openalex.org/W2134036641","authors":[],"funders":[],"total_grants":0,"fwci":2.06,"citation_percentile":0.87298326,"influential_citations":0,"citation_trend":[{"year":2012,"count":1},{"year":2013,"count":1},{"year":2017,"count":1},{"year":2019,"count":1},{"year":2021,"count":1},{"year":2025,"count":1}],"oa_status":"bronze","license":"https://academic.oup.com/pages/standard-publication-reuse-rights","oa_locations":[{"url":"https://journals.aai.org/jimmunol/article-pdf/170/3/1150/1161708/1150.pdf","host_type":"journal"},{"url":"https://journals.aai.org/jimmunol/article-pdf/170/3/1150/1161708/1150.pdf","host_type":"publisher"},{"url":"https://academic.oup.com/jimmunol/article-pdf/170/3/1150/62563916/1150.pdf","host_type":"publisher"},{"url":"https://doi.org/10.4049/jimmunol.170.3.1150","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/12538670","host_type":"repository"},{"url":"http://hdl.handle.net/2158/308946","host_type":"repository"},{"url":"https://iris.unil.ch/handle/iris/53883","host_type":"repository"},{"url":"https://serval.unil.ch/notice/serval:BIB_33B0D6CCD5D0","host_type":"repository"},{"url":"https://archive-ouverte.unige.ch/unige:11502","host_type":"repository"}],"fields_of_study":["Immune Cell Function and Interaction","T-cell and B-cell Immunology","Immunotherapy and Immune Responses"],"mesh_terms":["Adult","Animals","Cell Differentiation","Gene Expression Regulation","Genes, MHC Class II","Humans","Lymphocyte Activation","Mice, Inbred BALB C","Mice, Inbred CBA","Mice, Inbred C57BL","Mice, Transgenic","Nuclear Proteins","Species Specificity","CD4-Positive T-Lymphocytes","Trans-Activators","Cytokines","Th1 Cells","Th2 Cells","Mice"],"keywords":["Transactivation","MHC class II","Class (philosophy)","Expression (computer science)","MHC class I","Biology","Cell biology","Major histocompatibility complex","Immunology","Chemistry","Computer science","Gene expression","Genetics","Antigen","Gene","Artificial intelligence"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-11T10:41:56.048463Z","pmid":null,"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":[]}