Blockade of T cell activation induced by the simultaneous absence of Nod1 and Nod2 is bypassed by TLR2 signals.

Abstract

Pattern recognition receptors (PRRs) trigger adaptive inflammatory responses and as such are attractive targets for therapeutic manipulation of inflammation. In order to develop effective therapies however we need to understand the complexities of PRR signaling and clarify how individual PRRs contribute to an inflammatory response in a given cell type. Data from our lab and others have shown that cross-talk occurs between different PRR family members that directs T cell responses to a particular stimuli. It is well-established that the cell surface toll-like receptor 2 (TLR2) provides a potent costimulatory signal for TCR-stimulated T cell activation. We have shown that signaling through the intracellular nucleotide-binding oligomerization domain-containing proteins 1 and 2 (Nod1 and Nod2) also provides important signals for T cell activation, and that when both Nod1 and Nod 2 are deleted stimulated T cells undergo activation-induced cell death. This study found that TLR2 costimulation could bypass the defect induced by the simultaneous absence of Nods1 and 2 in both antibody- and antigen-stimulated T cells. Since blocking one set of PRR-mediated responses can be overcome by signaling through another PRR family member, then effective therapeutic immune blockade strategies will likely require a multi-pronged approach in order to be effective.

• Authors: Sashi Kasimsetty, Alana Hawkes, Sean E DeWolf, Alexander Welch, Dianne B McKay
• Journal: Transplant immunology (Transpl Immunol) Vol. 65 Pg. 101348 (04 2021) ISSN: 1878-5492 [Electronic] Netherlands
• PMID: 33706865 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2020. Published by Elsevier B.V.

Chemical References

• Nod2 Signaling Adaptor Protein
• Receptors, Pattern Recognition
• Toll-Like Receptor 2

Topics

• Lymphocyte Activation
• Nod2 Signaling Adaptor Protein (genetics, metabolism)
• Receptors, Pattern Recognition (metabolism)
• T-Lymphocytes
• Toll-Like Receptor 2 (metabolism)