Advances in understanding and managing celiac disease: Pathophysiology and treatment strategies

Figure 1 Pathophysiological mechanisms of celiac disease. Gluten or gliadin crosses the epithelial cells, and after the deamidation by transglutaminase-2 (TG2), they become easier to be recognized by antigen presenting cells (APCs) expressing HLA-DQ2/8. APCs could secrete interleukin (IL)-15 which causes damage to epithelial cells directly or through activation of intraepithelial lymphocytes expressing natural killer cell receptor. Also, APCs present the deamidated polypeptides complex to CD4⁺ T cells which further secrete interferon-γ and IL-21 to cause damage to epithelial cells. In another way, CD4⁺ T cells activate B cells to differentiate into plasma cells with secretion of antibodies against gluten, TG2, and deamidated polypeptides complex. TG2: Transglutaminase-2; IL: Interleukin; HLA: Human leukocyte antigen; APC: Antigen presenting cells; TCR: T cell receptor; IELs: Intraepithelial lymphocytes; IFN-γ: Interferon-γ; NKG2D: Natural killer cell receptor.