Laryngeal T regulatory cells in the setting of smoking and reflux

• Published in: The Laryngoscope 2017-04, Vol.127 (4), p.882-887
• Main Authors: Jetté, Marie E., Seroogy, Christine M., Thibeault, Susan L.
• Format: Article
• Language: English
• Subjects: Adult; Age Factors; Aged; Cross-Sectional Studies; Epigenetics; Female; Gastroesophageal Reflux - immunology; Gastroesophageal Reflux - physiopathology; Homeostasis - immunology; Humans; Immune Tolerance - physiology; Immunity, Mucosal - physiology; Laryngeal Mucosa - immunology; Laryngopharyngeal Reflux - immunology; Laryngopharyngeal Reflux - physiopathology; Larynx; Linear Models; Lymphocytes; Male; Middle Aged; mucosal immunity; Risk Assessment; Sex Factors; Smoking; Smoking - adverse effects; Smoking - immunology; T regulatory cell; T-Lymphocytes, Regulatory - immunology; vocal fold; Young Adult
• ISSN: 0023-852X; 1531-4995
• DOI: 10.1002/lary.26223

Objectives/Hypothesis The larynx is a mucosal organ rich in lymphatic tissue that is regularly exposed to a multitude of inhaled, ingested, and refluxed microorganisms and irritants. The first line of mucosal immune defense is the barrier, including resident immune cells. T regulatory (Treg) cells are a specialized subset of CD4+ T cells that suppress or dampen immune responses to prevent damaging immunopathology. As Treg cells have been shown to preferentially accumulate at sites of infection, and Treg responses may contribute to persistence of infection by impairing antibacterial immunity, we sought to quantify these cells in laryngeal tissue exposed to smoking and reflux. Study Design Cross‐sectional study. Methods Using an epigenetic assay, we quantified Treg and T cells and calculated the ratio of Treg to T cells (i.e., cellular ratio of immune tolerance [ImmunoCRIT]) in disease‐free laryngeal biopsies representing four inflammatory states: 1) tobacco‐exposed tissue, 2) refluxate and tobacco‐exposed tissue, 3) refluxate‐exposed tissue, and 4) unexposed tissue. Results There was epigenetic evidence of Treg cells in all tissues, and we found no differences in Treg cell frequency relative to smoking and reflux in laryngeal tissue collected from 42 non–treatment‐seeking participants. There was a decrease in total T cell frequency and an increase in ImmunoCRIT values in smokers regardless of reflux status. Conclusions In this study, laryngeal tissue from smokers show decreased overall T cells and increased ImmunoCRIT values. Our findings indicate that laryngeal inflammation is not directly mediated by loss of Treg cells in response to smoking and reflux in local tissue and increased ImmunoCRIT values in smokers implicate a role for this environmental exposure in modulating laryngeal immune homeostasis. More studies are indicated to explore Treg cell dysfunction in the pathophysiology of laryngeal disease. Level of Evidence NA Laryngoscope, 127:882–887, 2017