Migration-induced cell shattering due to DOCK8 deficiency causes a type 2-biased helper T cell response.

ABSTRACT: Mutations that impact immune cell migration and result in immune deficiency illustrate the importance of cell movement in host defense. In humans, loss-of-function mutations in DOCK8, a guanine exchange factor involved in hematopoietic cell migration, lead to immunodeficiency and, paradoxically, allergic disease. Here, we demonstrate that, like humans, Dock8^-/- mice have a profound type 2 CD4⁺ helper T (T_H2) cell bias upon pulmonary infection with Cryptococcus neoformans and other non-T_H2 stimuli. We found that recruited Dock8^-/-CX3CR1⁺ mononuclear phagocytes are exquisitely sensitive to migration-induced cell shattering, releasing interleukin (IL)-1β that drives granulocyte-macrophage colony-stimulating factor (GM-CSF) prod

SUBMITTER: Schneider C 

PROVIDER: S-EPMC10478007 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature