Cytokine routing as an overlooked determinant of immune mobilization

Route-dependent effects of GM-CSF on systemic and mucosal myeloid activation in rhesus macaques. Subcutaneous GM-CSF administration induced rapid systemic expansion of myeloid cells, accompanied by chemokine release (MCP-1, CXCL13 and IL-1RA) and enrichment of Fc receptor-bearing myeloid populations (CD64⁺ and CD32⁺) in circulation. These cells subsequently migrated to rectal and vaginal mucosa along chemokine gradients, resulting in sustained mucosal infiltration without overt systemic inflammation. In contrast, topical mucosal GM-CSF delivery elicited no detectable systemic expansion, chemokine induction or myeloid recruitment. Figure made in ©BioRender-biorender.com.