A CD4⁺ T cell-intrinsic complement C5aR2-prostacyclin-IL-1R2 axis orchestrates Th1 cell contraction.

ABSTRACT: T helper 1 (Th1) cell initiation pathways are well characterized; however, those regulating their contraction are less understood. Here, we define a CD4⁺ T cell-autonomous pathway in which complement C5 orchestrated a shift from prostaglandin E2 (PGE2) dominance to enhanced prostacyclin (PGI2) production via activation of C5a receptor 2 (C5aR2). This pivot in lipid mediators induced autocrine signaling through the PGI2 receptor and expression of the interleukin-1 (IL-1) decoy IL-1 receptor type 2 (IL-1R2), which sequestered Th1 cell-driving intrinsic IL-1β, facilitating Th1 cell contraction. Disruption of this C5aR2-PGI2-R axis was a hallmark of pathologically persistent Th1 cell activity in inflammatory conditions, including cryopyrin-associated periodic syndromes (CAPS), Crohn

SUBMITTER: Rahman J 

PROVIDER: S-EPMC12302006 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature