Blood and ileal T cell expression profiles differ in Crohn's disease

Last Updated: 2018-12-03

By Will Boggs MD

NEW YORK (Reuters Health) - T cells in peripheral blood and ileal biopsies show markedly different expression profiles in patients with Crohn's disease (CD), researchers report.

"Most interesting are the cytotoxic and Th17-like T cell populations in the intestinal mucosa from Crohn's disease patients, which show a clear overexpression of Crohn's disease risk genes, bearing out their importance in the disease," Dr. Eleonora A. Festen from University Medical Center Groningen, The Netherlands told Reuters Health.

"These important mucosal T cell populations are not reflected in the peripheral blood of the same patients at the same time points, showing that we should keep this tissue specificity in mind when studying and treating Crohn's disease," she said.

T cell signaling appears to be important in CD pathology, but there are few studies examining specific T cell types in the affected tissues.

Dr. Festen and colleagues performed flow cytometry and single-cell RNA sequencing of CD3-positive T cells isolated from peripheral blood T lymphocytes (PBL) and ileal biopsies of 3 CD patients with mild to moderate disease activity. The ileal biopsies included intraepithelial T lymphocytes (IEL) and lamina propria T lymphocytes (LPL).

They identified 6 distinct T-cell types with different distributions. Cytotoxic T lymphocytes (CTL) dominated the IEL, quiescent T cells dominated the PBL reservoir, and T-helper 17 (Th17) cells dominated the LPL, according to the November 1st Gastroenterology online report.

In peripheral blood, T-regulatory (Treg) cells intermixed with effector T cells and quiescent T cells, and Treg/quiescent cells were also present in the IEL and LPL.

Previously unidentified T cells expressing both CD3 and REG1A/B were present in both the IEL and LPL.

"Most surprising to me was the lack of a clear functional divide between CD4+ and CD8+ T cells in the intestinal mucosa of the Crohn's disease patients we studied," Dr. Festen said in an email. "While we did see the clear IL17-driven and cytotoxic populations we expected, these did not have any clear CD4+ or CD8+ phenotype that we expected them to have."

TH17 cells and CTL expressed additional genes whose products are targeted by drugs that are under development or have been approved for other indications.

"As a gastroenterologist treating Crohn's disease patients, these study results remind me once again to judge disease activity on assessment of the gastrointestinal mucosa (while of course always mindful of severe disease or drug side effects manifesting in the peripheral blood)," Dr. Festen said. "They also urge me to seek more specific treatment options, which I think will have to involve assessing the effect of commonly prescribed drugs on a tissue specific basis, and from this basis identifying new disease- and tissue-specific drug targets."

"We have focused on T cells alone and have identified two large groups of T cells in the two different layers of the intestinal mucosa that are highly relevant for Crohn's disease and highly specific to the intestinal mucosa," she said. "Study of the full array of cell types in the intestinal mucosa in Crohn's disease is likely to yield many more cell types with this intestinal specific profile."

SOURCE: http://bit.ly/2RxUl3O

Gastroenterology 2018.