How to deal with polarized Th2 cells: exploring the Achilles' heel.
The central effector cells in the pathogenesis of atopic allergic diseases are type 2 T helper (Th2) cells, which display an aberrant cytokine profile dominated by type 2 cytokines. Initial reports from mouse studies indicated that established and committed Th2 cells are stable and unsusceptible to modulation. However, there is a growing awareness that in humans, established effector Th2 cells are more flexible and can be reverted to predominant Th1 phenotypes. In fact, the Th1-driving cytokine interleukin (IL)-12 is the crucial factor in this respect. IL-12 is mainly produced by dendritic cells (DC), which can be primed for high or low IL-12 production, depending on inflammatory and/or microbial signals they encounter during their residence in the peripheral tissues. Accordingly, both the regulation of and the priming for IL-12 production in DC form ideal targets for therapeutic intervention. The development of new therapies for atopic allergy now focuses on local IL-12-promoting substances to target both the development of new Th2 cells and the persistent population of established allergen-specific Th2 cells.
Smits
H H
HH
Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, The Netherlands.
Hilkens
C M
CM
Kalinski
P
P
Kapsenberg
M L
ML
Wierenga
E A
EA
D000818:Animals; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000502:physiology*; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology*; D018664:Interleukin-12 / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D018123:Receptors, Interleukin / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000502:physiology; D018418:Th2 Cells / Q000276:immunology / Q000502:physiology*
D018123:Receptors, Interleukin; D018664:Interleukin-12