Innate Lymphoid Cells Groups 1 and 3 in the Epithelial Compartment of Functional Human Intestinal Allografts

Area of Science:

• Immunology
• Transplantation Science
• Gastroenterology

Background:

• Intraepithelial lymphocytes (IELs) play a crucial role in mucosal immunity.
• The composition and function of IELs in intestinal grafts post-transplantation are not fully understood.
• Understanding IEL dynamics is vital for improving graft survival and function.

Purpose of the Study:

• To characterize the IEL subsets in human intestinal grafts compared to native intestines.
• To investigate the phenotypic and functional differences of IELs in graft settings.
• To explore the potential role of IEL subsets in intestinal graft viability.

Main Methods:

• Analysis of 213 ileal biopsies from 16 bowel grafts and 32 native intestine biopsies.
• Flow cytometry to identify and quantify IEL subsets (e.g., CD103(+), CD3(+), CD8(+), CD3(-)).
• Ex vivo and in vitro functional assays to assess cytokine production (IFN-γ, IL-22) and cytotoxicity.

Main Results:

• Grafts showed reduced CD3(+) CD8(+) IELs and increased CD3(-) IELs in the first year post-transplantation.
• Graft CD3(-) IELs exhibited characteristics of natural killer (NK) cells and innate lymphoid cells (ILCs), expressing markers like CD56, NKp44, IL-23R, RORγt, and CCR6.
• Graft CD3(-) IELs produced higher levels of IFN-γ and IL-22, with a notable IFNγ(+) IL-22(+) population, and displayed cytotoxicity.

Conclusions:

• A distinct CD3(-) IEL subset, resembling ILC1 and ILC3, predominates in intestinal grafts.
• These IELs possess cytotoxic and cytokine-producing capabilities, potentially influencing graft immunity.
• The balance of pro-inflammatory and homeostatic ILC subsets may be critical for intestinal graft viability.