Neutrophil Biology: JAGN1 Deficiency is Responsible for Neutropenia

Granulocyte-Macrophage colony stimulating factor can salvage JAGN1 defect in bone marrow precursors causing congenital neutropenia. Neutrophils are the sentinel of host immune systems that are dispatched to surveil, engage and combat microbial pathogens. Neutropenic patients with low neutrophil counts are unable to mount neutrophil based immune responses and as a result become vulnerable to infections. JAGN1 encoding Jagunal homolog 1 expressed in hematopoietic progenitors and it’s deficiency makes neutrophil incompetent effector cells. In JAGN1 mutant mice, Penniger et al. demonstrated that the defect in JAGN1 function is rescued by granulocyte/ macrophage colony stimulating factor (GM-CSF) when afflicted by Candida albicans. JAGN1 mutant neutrophils are characterized by fewer granules, aberrant N-glycosylation of multiple protein patterns, apoptosis and are consequently unable to battle the pathogens. The authors showed that only GM-CSF helps in maturation of Myeloperoxide (MPO) containing secondary granules and thus, rescues the impaired reactive oxygen species (ROS) production [1]. The paper presented compelling evidence the JAGN1 defect was due to alterations in the Nglycosylation causing malfunction in neutrophil homing and effector roles [1,2]. Further, the study was extended in Severe Congenital Neutropenia (SCN) patients, whose bone marrow granulocytes was challenged with Candida, and then treated with GMCSF in vitro. It was, thus, established that this new-found neutrophil regulator, JAGN1, is responsible for congenital neutropenia [1,2].