Intraepithileal Lymphocytes and IL15
The release of IL15 is a major factor in coeliac disease as IL15 has been found to attract intraepithelial lymphocytes (IEL) that characterize Marsh grade 1 and 2 coeliac disease. Lymphocytes attracted by IL-15 are composed of markers enriched on natural killer cells versus normal helper T-cells. One hypothesis is that IL-15 induces the highly inflammatory Th1 response that activates T-helper cells (DQ2 restricted gliadin specific) that then orchestrate the destructive response, but the reason why inflammatory cells develop prior to gliadin specific helper cells is not known. The IRP response differs from typical responses that stimulate IL15 release, such as viral infection. In addition, other cytokines such as IL12 and IL2, which are typically associated with T-helper cell stimulation, are not involved. In these two ways the innate peptide activation of T-cells in celiac disease is strange. IL-15 appears to induce increases in MICA and NKG2D that may increase brush-border cell killing.
In addition, innate immunity to IRP peptide is involved in coeliac disease, dermatitis herpetiformis and possibly juvenile diabetes. IRP targets monocytes and increases the production of IL-15 by an HLA-DQ independent pathway, a subsequent study showed that both this region and the "33mer" could create the same response, in cells from both treated coeliacs and non-coeliacs. However, unlike the non-coeliacs, the treated coeliac cells produce the disease marker nitrite. This indicates that another abnormality in people with coeliac disease that allows stimulation to proceed past the normal healthy state. After extensive study, there is no known genetic association for this that appears to stand out at present, and implicates other environmental factors in the defect.