Intestinal reengineering: Scientific advances in intestinal transplantation

Table 1 Potential functions and mechanisms of immune cells in small intestine transplantation

Immune cell type	Infiltration characteristics and functions	Related mechanisms/molecular markers	Clinical significance	Ref.
T cell (CD8+)	Key effector cells in early AR; may develop exhausted-like phenotype under persistent antigen stimulation	PD-1, TIM-3, IFN-γ	AR biomarker; PD-1 inhibition must consider graft-vs-host disease risk	[209-211]
T cell (CD4+)	Th1/Th17 subsets drive rejection; Treg maintains mucosal homeostasis by suppressing inflammation	Th17: IL-17; Treg: FoxP3, IL-10, TGF-β	Th17/Treg ratio reflects rejection risk; modulating this axis improves outcomes	[91,92,212]
Regulatory T cells (Tregs)	Inhibit effector T cell activation; key regulatory cells promoting transplant tolerance	FoxP3, CTLA-4, IL-10, TGF-β	Treg expansion strategies may enhance tolerance and reduce rejection	[104,105,213]
B cell	Mediate chronic rejection and vascular injury via DSA production	IgG/IgM, complement activation, intimal hyperplasia	DSA levels correlate with chronic rejection; rituximab as therapeutic option	[164,214,215]
Natural Killer Cell (NK)	Contribute to rejection via ADCC; low-activity NK may support tolerance	NKG2D, perforin/granzyme, IL-10 inhibition	Regulating NK may reduce antibody-mediated rejection and mucosal injury	[101,216,217]
DC	Activate T cells in lymph nodes; tolerogenic DCs induce Treg differentiation	cDC1/cDC2 antigen presentation; pDC: IFN-α; tolerogenic DC: PD-L1	DC subpopulation imbalance promotes Th1 polarization; targeting PD-L1 can enhance transplant tolerance	[218-220]
Macrophage	M1 aggravates ischemia reperfusion injury; M2 promotes tissue repair and immune suppression	M1: TNF-α, IL-6; M2: ARG1	M1/M2 balance affects prognosis and barrier preservation	[221-224]
Mast cell	Disrupt mucosal barrier; associated with anastomotic leakage and infection	Histamine, IL-4, IL-13, eosinophil recruitment	Antihistamines or stabilizers may prevent complications	[225,226]
Myeloid inhibitory cells (MDSC)	Suppress T cell responses; excessive accumulation may lead to fibrosis	ARG1, ROS, M-MDSC	Targeted MDSC modulation needed to avoid immune imbalance	[227-229]
γδT cell	Regulate epithelial repair and microbial homeostasis; produce IL-17 and IL-22	γδT17 subset, IL-17, IL-22, villous regeneration	Support mucosal regeneration; crucial in post-ITx repair	[230,231]
ILC	ILC3 preserve epithelial integrity via IL-22; ILC2 mediate type 2 responses and may influence fibrosis	ILC3: RORγt, IL-22; ILC2: IL-5, IL-13	Dysfunction linked to chronic inflammation; IL-22 as repair target	[232,233]

AR: Acute rejection; PD-1: Programmed cell death 1; IFN: Interferon; DSA: Donor-specific antibody; DC: Dendritic cells; ILC: Innate lymphoid cells.