Abstract
Intestinal tissue-resident memory CD8 T cells (Trm) are non-recirculating effector cells ideally positioned to detect and react to microbial infections in the gut mucosa. There is an emerging understanding of Trm cell differentiation and functions, but their implication in inflammatory bowel diseases, such as Crohn's disease (CD), is still unknown. Here, we describe CD8 cells in the human intestine expressing KLRG1 or CD103, two receptors of E-cadherin. While CD103 CD8 T cells are present in high numbers in the mucosa of CD patients and controls, KLRG1 CD8 T cells are increased in inflammatory conditions. Mucosal CD103 CD8 T cells are more responsive to TCR restimulation, but KLRG1 CD8 T cells show increased cytotoxic and proliferative potential. CD103 CD8 T cells originate mostly from KLRG1 negative cells after TCR triggering and TGFβ stimulation. Interestingly, mucosal CD103 CD8 T cells from CD patients display major changes in their transcriptomic landscape compared to controls. They express Th17 related genes including CCL20, IL22, and IL26, which could contribute to the pathogenesis of CD. Overall, these findings suggest that CD103 CD8 T cells in CD induce a tissue-wide alert increasing innate immune responses and recruitment of effector cells such as KLRG1 CD8 T cells.
Highlights
Tcells differentiate from naive precursors after recognition of their specific antigen, [1] generating central and effector memory T cells (Tcm, Tem) which are defined by different functions [2, 3]
We assessed the expression of CD103 and KLRG1, two receptors of E-cadherin expressed by intestinal epithelial cells, on peripheral and mucosal CD8 T cells and saw an expected increased expression of CD103 on mucosal CD8 T cells compared to peripheral CD8 T cells
The inhibitory receptor NKG2A was co-expressed mainly by CD103 positive CD8 T cells in the mucosa (Figures 1C–E). Taken together these results suggest that expression of CD103 and KLRG1 markers could define functionally different subsets of CD8 T cells in the intestine
Summary
Tcells differentiate from naive precursors after recognition of their specific antigen, [1] generating central and effector memory T cells (Tcm, Tem) which are defined by different functions [2, 3]. Trm cell differentiation relies on the capacity of effector T cells to migrate into tissues and respond to local tissular cues, such as chemokines and adhesion molecules, produced constitutively or during infection and inflammation [9, 10]. The presence of the microbiota and foodborne antigens generate a tissular microenvironment that participates to the presence of T cells with specific features. Intestinal specific signals from the microbiota and inflammatory pathways, such as TGFβ or IL-15, have been suggested to regulate the phenotype and functions of Trm cells in the intestine [11,12,13]. T cells are rewired in situ following their recruitment in the gut and acquire new functions fitting to maintain intestinal homeostasis, respond to potential infections while preventing unnecessary immune responses to harmless protein antigens and commensal bacteria [9, 13,14,15]
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