CD28 is expressed by macrophages with anti‐inflammatory potential and limits their T‐cell activating capacity

Abstract

CD28 expression is generally considered to be T lymphocyte specific. We have previously shown CD28 mRNA expression in M‐CSF‐dependent anti‐inflammatory monocyte‐derived macrophages (M‐MØ), and now demonstrate that CD28 cell surface expression is higher in M‐MØ than in GM‐CSF‐dependent macrophages, and that macrophage CD28 expression is regulated by MAFB and activin A. In vivo, CD28 was found in tumor‐associated macrophages and, to a lower extent, in pro‐inflammatory synovial fluid macrophages from rheumatoid arthritis patients. Analysis of mouse macrophages confirmed Cd28 expression in bone‐marrow derived M‐MØ. Indeed, anti‐CD28 antibodies triggered ERK1/2 phosphorylation in mouse M‐MØ. At the functional level, Cd28KO M‐MØ exhibited a significantly higher capacity to activate the OVA‐specific proliferation of OT‐II CD4+ T cells than WT M‐MØ, as well as enhanced LPS‐induced IL‐6 production. Besides, the Cd28KO M‐MØ transcriptome was significantly different from WT M‐MØ regarding the expression IFN response, inflammatory response, and TGF‐β signaling related gene sets. Therefore, defective CD28 expression in mouse macrophages associates to changes in gene expression profile, what might contribute to the altered functionality displayed by Cd28KO M‐MØ. Thus, CD28 expression appears as a hallmark of anti‐inflammatory macrophages and might be a target for immunotherapy.

Macrophage re-programming by JAK inhibitors relies on MAFB

“…1 D, Supplementary Table S1). On the other hand, the 129 genes whose expression is augmented upon Upa treatment included several genes associated to anti-inflammatory functions like CD28 and CD127 [ 39 , 40 ] (Fig. 1 D, Supplementary Table S1).…”

Silencing miR-146a-5p Protects against Injury-Induced Osteoarthritis in Mice

“…Cd28, previously known as a paradigmatic T-cell co-stimulator, is identified not exclusively in T cells but also in other cell types. For instance, CD28-expressed macrophages exhibit a potent anti-inflammatory potential that limits their T-cell stimulatory capacity [51]. Prkg1, on the other hand, has recently been suggested to exert an anti-inflammatory reaction by reducing NF-κB activity and Il1b and Nlrp3 gene transcription in the liver [52].…”