Foxp3+ Tregs from Langerhans cell histiocytosis lesions co-express CD56 and have a definitively regulatory capacity

• Published in: Clinical immunology (Orlando, Fla.) Vol. 215; p. 108418
• Main Authors: Mitchell, Jenée, Kelly, Jason, Kvedaraite, Egle, von Bahr Greenwood, Tatiana, Henter, Jan-Inge, Pellicci, Daniel G., Berzins, Stuart P., Kannourakis, George
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2020
• Subjects: Adolescent; Adult; Aged; CD56 Antigen - immunology; CD8-Positive T-Lymphocytes - immunology; Child; Child, Preschool; Cytotoxic T cells; Female; Forkhead Transcription Factors - immunology; Foxp3+ Tregs; Histiocytosis, Langerhans-Cell - immunology; Humans; Infant; Inflammation - immunology; Langerhans cell histiocytosis; Langerhans Cells - immunology; LCH; Male; Medicin och hälsovetenskap; Middle Aged; T-Lymphocytes, Regulatory - immunology; TGF-β; Transforming Growth Factor beta - immunology; Tregs; LCH; TGF-β; Langerhans cell histiocytosis; Tregs; Foxp3+ Tregs; Cytotoxic T cells; Foxp3(+) Tregs
• ISSN: 1521-6616; 1521-7035; 1521-7035
• DOI: 10.1016/j.clim.2020.108418

Langerhans cell histiocytosis (LCH) lesions contain myeloid lineage ‘LCH’ cells. Regulatory T cells (Tregs) are also enriched within lesions, although their role in LCH pathogenesis is unknown. LCH cells are thought to produce the transforming growth factor beta (TGF-β) within lesions, however whether Tregs contribute is unestablished. Using flow cytometry, we analyzed relative frequencies of live Tregs from LCH patients and identified CD56 expression and TGF-β production by lesion Tregs. While CD56+ Tregs were enriched in lesions, overall CD56+ T cells were reduced in the blood from active LCH patients compared to non-active disease patients, and there was a negative correlation between CD8+CD56+ T cells and Tregs. We propose that inducing a Treg phenotype in T cells such as CD56+ T cells may be a mechanism by which LCH cells divert inflammatory T cell responses. Thus, Tregs within LCH lesions are likely an important component in LCH pathogenesis. •Foxp3+ Tregs from Langerhans cell histiocytosis lesions co-express CD56•Foxp3+ Tregs from Langerhans cell histiocytosis lesions produce TGF-β•Treg enrichment in LCH patients is associated with reduced CD8+CD56+ T cells