Functions of TRPM7 chanzyme in Innate and Adaptive Immunity

Stremska, Marta, Microbiology - School of Medicine, University of Virginia
Desai, Bimal, MD-PHAR Pharmacology, University of Virginia
Ravichandran, Kodi, University of Virginia
Ewald, Sarah, MD-MICR Microbiology, University of Virginia
Bochkis, Irina, MD-PHAR Pharmacology, University of Virginia
Hahn, Young, MD-MICR Microbiology, University of Virginia

Innate and adaptive immune cells orchestrate inflammatory responses in the host to protect against invading pathogens. Innate immune cells recognize pathogen-derived molecules to mount inflammation, sequester and kill microbes and present their antigens to T cells. Adaptive immune responses are precisely directed towards presented antigens and take time to develop upon the first encounter, however, the response time shortens during consecutive confrontations with the same invader. A specialized subtype of T cells, regulatory T cells (Tregs), suppress excessive inflammation and promote immune and tissue homeostasis. All immune cells integrate multiple signals upon ligand stimulation. Calcium (Ca2+) serves important roles as a second messenger, drives cell activation and signaling pathways of pro-and anti-inflammatory programs. Recent studies have been defining electrical signaling as a key component immune cell function. TRP-superfamily of ion channels comprises a group of multifunctional proteins with many roles in sensory perception and cellular physiology. This work describes the roles of one highly conserved member, TRPM7, in innate and adaptive immunity. In macrophages, TRPM7-activated current is triggered upon recognition of a fungal particle and the chanzyme’s activity is important in effective fungal phagocytosis. TPRM7-deficient T cells display a developmental block, overproduce IL-2 and display increased Treg:Teff ratio.

PHD (Doctor of Philosophy)
TRPM7, Chanzyme, phagocytosis, yeast, macrophage, Treg, IL-2
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