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In human immunodeficiency virus (HIV) infection, functional defects and deletion of antigen-reactive T cells are more frequent than can be explained by direct viral infection. On culturing, both CD4 ⁺ and CD8 ⁺ T cells from asymptomatic HIV-infected individuals died as a result of programmed cell death (apoptosis). Apoptosis was enhanced by activation with CD3 antibodies. Programmed cell death, associated with impaired T cell reactivity, may thus be responsible for the deletion of reactive T cells that contributes to HIV-induced immunodeficiency.

Collagens are the most abundant proteins in the human body, important in maintenance of tissue structure and hemostasis. Here we report that collagens are high affinity ligands for the broadly expressed inhibitory leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1). The interaction is dependent on the conserved Gly-Pro-Hyp collagen repeats. Antibody cross-linking of LAIR-1 is known to inhibit immune cell function in vitro. We now show that collagens are functional ligands for LAIR-1 and directly inhibit immune cell activation in vitro. Thus far, all documented ligands for immune inhibitory receptors are membrane molecules, implying a regulatory role in cell–cell interaction. Our data reveal a novel mechanism of peripheral immune regulation by inhibitory immune receptors binding to extracellular matrix collagens.

The immune system protects the body from invaders such as viruses and bacteria. Immune cells must be activated in the correct context to function properly. It is critical that the receptors, costimulatory molecules, and cytokines that orchestrate this activation are carefully regulated to prevent uncontrolled inflammation and autoimmunity. Inhibitory receptors play an important role in regulation of immune cell function, usually upon interaction with ligands present on other cells. In contrast, the function of the inhibitory leukocyte-associated Ig-like receptor (LAIR)-1 can be regulated by extracellular matrix collagens. LAIR-1 is expressed on most cells of the immune system, and its function has been studied on multiple cell types. This review summarizes current literature about LAIR-1, a receptor that potentially is able to regulate multiple steps of an immune response.

The current paradigm is that inflammatory pain passively resolves following the cessation of inflammation. Yet, in a substantial proportion of patients with inflammatory diseases, resolution of inflammation is not sufficient to resolve pain, resulting in chronic pain. Mechanistic insight into how inflammatory pain is resolved is lacking. Here, we show that macrophages actively control resolution of inflammatory pain remotely from the site of inflammation by transferring mitochondria to sensory neurons. During resolution of inflammatory pain in mice, M2-like macrophages infiltrate the dorsal root ganglia that contain the somata of sensory neurons, concurrent with the recovery of oxidative phosphorylation in sensory neurons. The resolution of pain and the transfer of mitochondria requires expression of CD200 receptor (CD200R) on macrophages and the non-canonical CD200R-ligand iSec1 on sensory neurons. Our data reveal a novel mechanism for active resolution of inflammatory pain.