Table 4.

Involvement of CD26/dipeptidyl peptidase 4 (DPP4) in T helper type 1 (Th1) and Th2 responses 3, 17, 49, 67, 81, 88, 112, 116, 188, 189, 190, 191, 192.

	Th1	Th2
CD26 expression	High expression on CD26bright memory T cell subset Binding of caveolin‐1 on dentritic APC cells to CD26 on Th1 cells, results in binding of CARMA‐1 cytoplasmic tail of CD26 ⇒ recruitment of CARMA‐1, CD26, Bcl10 and IkappaB kinase complex to lipid rafts ⇒ signal transduction ⇑ up‐regulation of CD26 expression upon induction of Th1 response	Slight up‐regulation of CD26 expression
Subcellular compartmentation	Association of CD26 to lipid rafts Binding of CD26 to CD45R0+ on lipid rafts, resulting in signal transduction; followed by disassembly of CD45R0 from lipid rafts	Binding of CD26 to M6P/IGFIIR ⇒ internalization + T cell activation Association of CD26 + CXCR4 ⇒ internalization
Chemokine DPP4 substrates	CXCR3 → IP‐10 CCR1 → RANTES1–68 > RANTES3–68 CCR5 → RANTES3–68 > RANTES 1‐68	CXCR4 → SDF‐1α1–68 > SDF‐1α3–68 CCR3 → eotaxin1–74 > eotaxin3–74 CCR4 → MDC1–67 ≠ MDC3–67 CCR1 → RANTES1–68 > RANTES3–68 CCR3 → RANTES3–68 > RANTES 1–68
Neuropeptide/peptide DPP4 substrates	NPY released from SNS involved in inflammatory response of macrophages, NK and T cells GLP‐2 involved in Crohn's disease	Mast‐cells: substanceP → allergy + asthma NPY released from SNS involved in inflammatory response of PMN and B cells
Inflammatory response	Soluble DPP4 found in secretory lysosomes of TC cells Membrane‐bound DPP4 in secretory lysosomes of NK cells ⇑ DPP4 on activated macrophages truncate NPY → loss of Y1‐R binding → ⇓ IL‐1β and IL‐6 release ⇑ DPP4 on activated microglia	T cell recruitment in asthma is DPP4‐dependent
Site of inflammation	Arthritis: ⇑ DPP4 on activated synoviocytes + CD26 internalized via caveolae ⇑ hypersialylation of DPP4 → ⇓ sDPP4 activity → ⇑ SDF‐α → ⇑ inflammation ⇑ DPP4 on endothelial cells via IFN‐γ, TNF‐α and LPS stimulation Crohn's disease: ⇑ DPP4 in enterocytes → ⇓ GLP‐2 ⇑ DPP4 on activated microglia + astrocytes after ischaemia	Asthma: ⇑ DPP4 in lung parenchyma Binding of CD26 to M6P/IGFIIR → transendothelial migration of lymphocytes
Diseases associated with DPP4/CD26	Rheumatoid arthritis Multiple sclerosis Truncation of RANTES by DPP4 → ⇑ protection against HIV entry Ischaemia	Truncation of SDF‐1α by DPP4 → ⇓ protection against HIV entry CD26+ T cells involved in the pathogenesis of asthma correlating to IgE titre of antigen