Abstract
Abstract Natural killer (NK) cells are specialized lymphocytes with innate ability to eliminate virally infected and cancerous cells. NK cells stochastically express Ly49 activating and inhibitory surface receptors, through mechanisms that are not fully understood. Ly49 expression during NK cell development is regulated by a combination of external and internal factors, such as major histocompatibility complex class I (MHC-I) ligands and cytokines. Global deletion of sclerostin domain containing-1 (Sostdc1), a secreted protein, leads to altered bone homeostasis via dysregulation of Wnt and BMP signaling, which in turn, could result in altered immune cell development in the bone marrow (BM). Using Sostdc1-knockout (KO) mice, we have discovered a novel role for Sostdc1 in NK cell development. Flow cytometric analysis of the Ly49 repertoire in immature (CD27+CD11b-; iNK), transitional (CD27+CD11b+, tNK) and most mature (CD27-CD11b+, mNK) Sostdc1-KO NK cells demonstrated expression differences in Ly49G2, I, H, and D receptors. We also observed a progressive increase in tNK cell numbers and frequencies as the KOs aged from 12 weeks to 30 weeks, indicating a slowing or partial block in NK cell maturation with aging. Reciprocal BM chimera experiments showed that Sostdc1 regulates NK cells through cellintrinsic and cell-extrinsic manners. Consistent with this, Sostdc1 is expressed in the bone periosteum and we discovered Sostdc1 expression in CD45+ NK1.1-CD11b+ BM cells and iNK cells. Taken together, these data support a role for Sostdc1 in the regulation of NK cell differentiation and identify potential NK cell niches. Current studies are investigating whether Sostdc1-KO NK cells respond to stimulation and lyse MHC-I deficient target cells.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call