Immune cells are maintained in homeostasis, that is a relatively conserved stoichiometry which is altered during disease, and is returned to following. In disease state, while the system recovers, patients are at a high risk of infection since their ability to mount an immune response is drastically reduced, with a high fraction of chemotherapy treated patients dying due to lack of immune system reconstitution. Identification of “driver” molecules which can yield an increase in hematopoiesis rate through targeted cell-specific proliferation, may accelerate the process of recovery of the immune system. Secreted proteins (e.g. cytokines, integrins etc.) are known to have a key role in numerous immune processes by mediating immune interactions, are crucial for hematopoietic recovery as they serve as key factors for the expansion of the progenitor populations. To identify external molecular drivers which affect cellular balance in non-steady state conditions, we undertook a Systems Immunology approach using genetically-diverse mouse strains whose high phenotypic variation allows association of cell subset frequencies in the bone marrow, measured in high dimensions by mass cytometry, with the abundance of multiple serum proteins. We came up with a list of candidate proteins that may drive the process of immune system recovery, which we further narrowed by cross-referencing databases of gene expression profiling and known inter-cellular interactions. Testing such predictions in-vitro and in-vivo leads to validation of the crucial role of molecular drivers in increasing hematopoiesis by specifically pushing bone-marrow progenitors towards differentiation and replenishing the immune cells milieu.