The anti-inflammatory effects of 1,25-dihydroxyvitamin D3 on Th2 cells in vivo are due in part to the control of integrin-mediated T lymphocyte homing.
The fat soluble vitamin D3 metabolite 1,25-dihydroxyvitamin D3 [1,25(OH)(2)D(3)], and its nuclear receptor play an important role in regulating immune responses. While 1,25(OH)(2)D(3 )is known to inhibit transcription of cytokine genes that are required for Th1 differentiation or are products of differentiated Th1 cells, its role in regulating differentiation of Th2 cells is less clear. In this study, we show that 1,25(OH)(2)D(3) has anti-inflammatory effects in an in vivo Th2-dependent asthma model. In addition, we demonstrate that 1,25(OH)(2)D(3 )down-regulates the cytoskeleton rearrangement required for promoting integrin-mediated adhesion of naive and effector CD4(+) T cells. Finally, 1,25(OH)(2)D(3 )inhibits chemokine-induced migration of naive cells and their homing to the lymph nodes. Thus, in addition to its regulation of cytokine transcription, 1,25(OH)(2)D(3 )regulates migration of cells and thus controls the skewing of various Th subsets in the secondary lymphoid organs and inhibits Th function at sites of inflammation.
Topilski
Ian
I
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
Flaishon
Liat
L
Naveh
Yaron
Y
Harmelin
Alon
A
Levo
Yoram
Y
Shachar
Idit
I
D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000276:immunology* / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002117:Calcitriol / Q000494:pharmacology*; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D003599:Cytoskeleton / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D007249:Inflammation / Q000276:immunology; D016023:Integrins / Q000276:immunology*; D015847:Interleukin-4 / Q000032:analysis; D008168:Lung / Q000276:immunology* / Q000473:pathology; D051379:Mice; D010047:Ovalbumin / Q000276:immunology / Q000633:toxicity; D018418:Th2 Cells / Q000276:immunology*
D016023:Integrins; D015847:Interleukin-4; D010047:Ovalbumin; D002117:Calcitriol