Organogenesis of lymphoid tissues.

The development of lymphoid organs depends on the correct expression of several molecules within a defined timeframe during ontogeny. Although this is an extremely complex process, with each secondary lymphoid tissue requiring subtly different signals, a common framework for lymphoid development is beginning to emerge. Drawing on studies of lymph nodes, Peyer's patches and nasal-associated lymphoid tissue, an integrative model of lymphoid-tissue development, involving adhesion molecules, cytokines and chemokines, which emphasizes the role of interactions between CD3-CD4+CD45+ 'inducer' cells and VCAM1+ICAM1+ stromal 'organizer' cells is presented

TRPA1

The transient receptor potential ankyrin subtype 1 protein (TRPA1) is a nonselective cation channel permeable to Ca2+, Na+, and K+. TRPA1 is a promiscuous chemical nocisensor that is also involved in noxious cold and mechanical sensation. It is present in a subpopulation of Aδ- and C-fiber nociceptive sensory neurons as well as in other sensory cells including epithelial cells. In primary sensory neurons, Ca2+ and Na+ flowing through TRPA1 into the cell cause membrane depolarization, action potential discharge, and neurotransmitter release both at peripheral and central neural projections. In addition to being activated by cysteine and lysine reactive electrophiles and oxidants, TRPA1 is indirectly activated by pro-inflammatory agents via the phospholipase C signaling pathway, in which cytosolic Ca2+ is an important regulator of channel gating. The finding that non-electrophilic compounds, including menthol and cannabinoids, activate TRPA1 may provide templates for the design of non-tissue damaging activators to fine-tune the activity of TRPA1 and raises the possibility that endogenous ligands sharing binding sites with such non-electrophiles exist and regulate TRPA1 channel activity. TRPA1 is promising as a drug target for novel treatments of pain, itch, and sensory hyperreactivity in visceral organs including the airways, bladder, and gastrointestinal tract