Neural-Cadherin Influences the Homing of Terminally Differentiated Memory CD8 T Cells to the Lymph Nodes and Bone Marrow

Abstract

Memory T (T M ) cells play an important role in the long-term defense against pathogen reinvasion. However, it is still unclear how these cells receive the crucial signals necessary for their longevity and homeostatic turnover. To understand how T M cells receive these signals, we infected mice with lymphocytic choriomeningitis virus (LCMV) and examined the expression sites of neural cadherin (N-cadherin) by immunofluorescence microscopy. We found that N-cadherin was expressed in the surroundings of the white pulps of the spleen and medulla of lymph nodes (LNs). Moreover, T M cells expressing high levels of killer cell lectin-like receptor G1 (KLRG1), a ligand of N-cadherin, were co-localized with N-cadherin + cells in the spleen but not in LNs. We then blocked N-cadherin in vivo to investigate whether it regulates the formation or function of T M cells. The numbers of CD127 hi CD62L hi T M cells in the spleen of memory P14 chimeric mice declined when N-cadherin was blocked during the contraction phase, without functional impairment of these cells. In addition, when CD127 lo KLRG1 hi T M cells were adoptively transferred into anti-N-cadherin-treated mice compared with control mice, the number of these cells was reduced in the bone marrow and LNs, with out functional loss. Taken together, our results suggest that N-cadherin participates in the development of CD127 hi CD62L hi T M cells and homing of CD127 lo KLRG1 hi T M cells to lymphoid organs.

The role of KLRG1: a novel biomarker and new therapeutic target

“…Although human T-cells also express KLRG1 and have the AMPK signaling pathway [61], it is unclear whether KLRG1 plays a similar role in T-cells. In addition, KLRG1 can bind to membranebound N-cad, recruiting SHIP-1 and SHP-2, inhibiting NK cell and T-cell function, and inducing cardiac endothelial cell proliferation and angiogenesis [62,63]. Moreover, KLRG1 can also cause functional depletion of NK cells by binding to soluble N-cad released by circulating tumor cells in a noncontact cell-cell manner [48,64].…”

SMAD4 promotes formation of terminally differentiated CTLs that localize in the microvasculature of the lungs but are excluded from the lumen of the airways

“…During EMT, stromal cells acquire migratory properties as epithelial (E)-Cadherin is down regulated by TGFβ, while neural (N)-cadherin is induced(10, 11). Both cadherins provide binding sites for adhesion molecules that are expressed on different subsets of antigen experienced CTLs (12, 13). Killer cell lectin-like receptor G1 (KLRG1) is an inhibitory receptor with a tyrosine-based inhibitory motif in the cytoplasmic domain and is expressed on terminally differentiated T EFF cells(14, 15), whereas CD103 (αEβ7 integrin) is expressed on naïve CD8 T cells and large numbers of noncirculating T RM cells (T RM )(3, 16).…”