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Celiac.com 08/16/2016 - Celiac disease changes the composition and differentiation potential of the duodenal intraepithelial innate lymphocyte compartment, specifically, the composition and function of duodenal intraepithelial T cells. The intestinal tract is also home to four types of CD3-negative intraepithelial lymphocytes (IELs) with largely unknown function: CD56(-)CD127(-); CD56(-)CD127(+); CD56(+)CD127(-) and CD56(+)CD127(+). A team of researchers wanted to gain insight into the potential function of these innate IELs in health and disease. Specifically, they wanted to assess how the composition and differentiation potential of the duodenal intraepithelial innate lymphocyte compartment is altered in celiac disease. The research team included F Schmitz, Y Kooy-Winkelaar, AS Wiekmeijer, MH Brugman, ML Mearin, C Mulder, S Chuva de Sousa Lopes, CL Mummery, FJ Staal, J van Bergen, F Koning. They are variously affiliated with the Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands, the Department of Immunohematology and Blood Transfusion at Leiden University Medical Center in Leiden, The Netherlands, the Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands, the Department of Gastroenterology at the Free University Medical Center, Amsterdam, The Netherlands, and with the Department of Anatomy and Embryology at Leiden University Medical Center in Leiden, The Netherlands. For their study, the team measured the phenotypes, relative abundance and differentiation potential of these innate IEL subsets in duodenal biopsies from controls and patients with celiac disease or patients with refractory celiac disease type II (RCDII). Hierarchical clustering analysis of the expression of 15 natural killer and T cell surface markers showed that innate IELs differed markedly from innate peripheral blood lymphocytes and divided innate IEL subsets into two main branches: a CD127(-) branch expressing high levels of interleukin (IL) 2/15Rβ but no IL-21R, and a CD127(+) branch with the opposite phenotype. While celiac disease was characterized by the contraction of all four innate IEL subsets, a selective expansion of CD56(-)CD127(-) and CD56(-)CD127(+) innate IEL was detected in RCDII. In vitro, in the presence of IL-15, CD56(-)CD127(-) IEL from controls and patients with celiac disease differentiated into functional natural killer and T cells, the latter largely dependent on notch-signaling. This did not occur in patients with RCDII. Furthermore, compared with non-celiac controls, CD56(-)CD127(-) IEL from patients with celiac disease expressed more intracellular CD3ε and CD3γ and gave more pronounced T cell differentiation. RCDII changes the normally diverse and plastic innate IEL compartment, and encourages a loss of differentiation potential. Source: Gut. 2016 Aug;65(8):1269-78. doi: 10.1136/gutjnl-2014-308153.
Celiac.com 01/04/2013 - Currently, doctors must still use invasive techniques to distinguish between uncomplicated and complicated forms of celiac disease. In an effort to find a non-invasive approach to the issue, a research team recently set out to investigate the potential use of novel serum parameters, including IL-6, IL-8, IL-17, IL-22, sCD25, sCD27, granzyme-B, sMICA and sCTLA-4 in patients diagnosed with active celiac disease, celiac disease on a GFD, Refractory coeliac disease (RCD) type I and II, and enteropathy associated T-cell lymphoma (EATL). The research team included Greetje J. Tack, Roy L. van Wanrooij, B. Mary Von Blomberg, Hedayat Amini, Veerle M. Coupe, Petra Bonnet, Chris J. Mulder and Marco W. Schreurs. Their investigation revealed elevated levels of the pro-inflammatory IL-8, IL-17 and sCD25 in both active celiac disease and in refractory celiac disease, types I and II. They also found that RCDII patients displayed higher serum levels of soluble granzyme-B and IL-6 in comparison to active celiac disease patients. Furthermore, EATL patients showed higher levels of IL-6 as compared to all other groups. Otherwise, the team found no differences between RCDI and active celiac disease or RCDII. These novel serum parameters show distinct immunological differences in RCDII and EATL, compared with uncomplicated celiac disease and RCDI. Source: BMC Gastroenterology 2012, 12:159. doi:10.1186/1471-230X-12-159