Zarrin, A. A. | Search bioRxiv

bioRxiv2024

Layilin Regulates Treg Motility and Suppressive Capacity in Skin

Regulatory T cells (Tregs) are essential for maintaining immune tolerance in both lymphoid and non-lymphoid tissues. We discovered that layilin, a C-type lectin receptor, is predominantly expressed on Tregs in skin. Layilin was highly expressed on a subset of clonally expanded effector Tregs in both healthy and psoriatic skin. Layilin expressing Tregs exhibited a transcriptional profile indicative of enhanced adhesion. Deletion of layilin in Tregs in vivo resulted in significantly attenuated skin inflammation. Mechanistically, layilin enhanced Treg adhesion via modulation of LFA-1, resulting in distinct cytoskeletal alterations consistent with enhanced focal adhesion and lamellipodia formation. Taken together, we define layilin as a critical regulator of Treg suppressive capacity through modulating motility and adhesion in a non-lymphoid tissue.

immunology↗

bioRxiv2018

Paired Immunoglobulin-like Type 2 Receptor Alpha G78R variant alters ligand binding and confers protection to Alzheimer’s disease

Paired Immunoglobulin-like Type 2 Receptor Alpha (PILRA) is a cell surface inhibitory receptor that recognizes specific O-glycosylated proteins and is expressed on various innate immune cell types including microglia. We show here that a common missense variant (G78R, rs1859788) of PILRA is the likely causal allele for the confirmed Alzheimers disease risk locus at 7q21 (rs1476679). The G78R variant alters the interaction of residues essential for sialic acid engagement, resulting in >50% reduced binding for several PILRA ligands including a novel ligand, complement component 4A, and herpes simplex virus 1 (HSV-1) glycoprotein B. PILRA is an entry receptor for HSV-1 via glycoprotein B, and macrophages derived from R78 homozygous donors showed significantly decreased levels of HSV-1 infection at several multiplicities of infection compared to homozygous G78 macrophages. We propose that PILRA G78R protects individuals from Alzheimers disease risk via reduced inhibitory signaling in microglia and reduced microglial infection during HSV-1 recurrence.

genetics↗