Microdevice integrating innate and adaptive immune responses associated with antigen presentation by dendritic cells

Abstract

Dendritic cells are the principal antigen presenting cells that are responsible for acquiring and transporting antigen from the peripheral tissue to the secondary lymphoid tissue. There they present it to T cells which ultimately initiate an antigen specific immune response. In vivo, the migration of dendritic cells (DCs) and T cell activation are intimately linked. However, ex vivo systems that facilitate integrated evaluation of DC chemotaxis and resulting T cell activation by migrated DCs are lacking. In this work, we have developed a microfabricated platform that integrates DC chemotaxis with T cell activation. The basic design of the microdevice includes two layers of PDMS, with the top layer comprising the chemotaxis compartment and the bottom layer containing a T cell compartment. In the chemotaxis compartment, the DCs are subjected to a chemokine gradient, and their migratory response is evaluated. In the T cell compartment, rapid DC-induced activation of T cells is evaluated by measuring the level of calcium in T cells. We demonstrate the efficacy of our approach by evaluating the integrated response of mature DCs, whereby the overall T cell activation response is governed both by the chemotaxis and the T cell activation potential of mature DCs relative to immature DCs. Our system provides a powerful platform for systematically probing various aspects of antigen induced immune responses – DC maturation, migration and T cell activation – in an integrated fashion.

Inhibition of IRF4 in dendritic cells by PRR-independent and -dependent signals inhibit Th2 and promote Th17 responses

“…We also checked the effect of cAMP in human DC-like cell lines generated from MUTZ-3 (myelomonocyte) (Mitra et al, 2013), THP-1 (monocyte) (Berges et al, 2005), and HL-60 (promyeloblast) (Koski et al, 1999). As observed with mouse cDC2s or BM-APCs, the human DC-like cells responded to CPT with a decrease in expression of Irf4 and Klf4 (Figure 2).…”

Immune Organs and Immune Cells on a Chip: An Overview of Biomedical Applications

“…This LNoC model thus allowed for the investigation of pMHC–T-cell receptor bonding mechanisms under controlled microenvironmental conditions. More studies have been performed to evaluate DC–T-cell interactions using LNoC models that were introduced in Table 1 [ 49 , 50 ].…”

3D Immunocompetent Organ‐on‐a‐Chip Models

“…Similarly, to mimic the migration of DCs and antigen presentation to T cells in the lymph node, a microfabricated system was developed. [ 79 ] This device consisted of top DC and bottom T‐cell compartments. The DCs were subjected to a chemokine CCL19 gradient, and migration of these DCs toward the T cell compartment was monitored.…”