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Complementarities of the Regulators

  1. Top of page
  2. Complementarities of the Regulators
  3. A New Approach for Artificial Activation of Signaling Molecules

B-cell depletion therapy (BCDT) has emerged as a promising approach for the treatment of autoimmune diseases. However, in addition to their pathogenic activities, B cells also have protective functions, associated primarily with their capacity to stimulate Foxp3+ natural regulatory T (Treg) cells, an important immunosuppressive cell type. Thus, BCDT might result not only in elimination of pathogenic B cells but also in reduced Treg cell-mediated protection. Hoehlig et al. address this potential concern, asking whether the activation of Treg cells depends on B cells during autoimmune disease, in this case EAE. The authors show that Tregcell activation proceeds normally in the complete absence of B cells, indicating that impaired Treg-cell function is an unlikely outcome of BCDT. In contrast, this study suggests that B cells and Treg cells provide two distinct layers of regulation that are both essential for the limitation of autoimmune pathology.

Hoehlig et al., Eur J Immunol 2012;42:1164–1173.

A New Approach for Artificial Activation of Signaling Molecules

  1. Top of page
  2. Complementarities of the Regulators
  3. A New Approach for Artificial Activation of Signaling Molecules

A system for artificial activation of target intracellular signaling molecules would be a valuable tool to attain functional analysis of proteins and tissue engineering through the control of cellular fates. Saka and coworkers developed a series of antibody/receptor chimeras enabling activation of target signaling molecules by an inexpensive non-toxic antigen. The chimeric receptors are superior to conventional tools -they can activate endogenous signaling molecules and modulate the activation levels by changing the concentration of a bioorthogonal ligand, antigen, at desired time points, and by utilizing specific tyrosine motifs that could specifically recruit the target signaling proteins, the combination of signaling pathways and networks activated via chimeric receptors can be artificially designed. This new approach expands the possibility of artificial activation of proteins which are difficult to control by conventional methods. Their report demonstrated that the chimeric receptors incorporating each tyrosine motif can activate the corresponding signaling molecules. Future work will aim to control activation of target molecules more specifically.

Saka et al., Biotechnol Bioeng 2012;109:1528–1537.