CD72-semaphorin3A axis: a possible new player in immune regulation

Abstract

Semaphorin3A (sema3A) inhibits the activity of B and T cells in autoimmune diseases such as Systemic Lupus Erythematosus (SLE). We have now found that CD72 functions as a novel sema3A binding and signal-transducing receptor. These functions of CD72 are independent of the known sema3A receptor neuropilin-1 (NRP-1). We find that sema3A induces the phosphorylation of CD72 on tyrosine residues and the association of CD72 with SHP-1 and SHP-2. In contrast, sema4D/CD100 inhibits these functions. sema3A signals mediated by CD72, inhibit the phosphorylation of STAT-4 and HDAC-1 and induce the phosphorylation of p38-MAPK and PKC-theta in B-cells derived B-lymphoblastoid (BLCL) cells lacking NRP-1 expression, and in primary B-cells isolated from either healthy donors or SLE (Systemic Lupus Erythematosus) patients. We have also generated a modified truncated sema3A (T-sema3A) which cannot signal via NRP-1 yet still activates inhibitory CD72 signaling. We propose that T-sema3A may have potential as a possible therapeutic for autoimmune diseases such as SLE. One Sentence SummaryCD72 found as a novel sema3A receptor transduces inhibitory signals in Bcells. A modified sema3A can be used to treat autoimmunity.