TY - JOUR
T1 - Innate immunity modulates autoimmunity
T2 - Type 1 interferon-β treatment in multiple sclerosis promotes growth and function of regulatory invariant natural killer T cells through dendritic cell maturation
AU - Gigli, Gianluigi
AU - Caielli, Simone
AU - Cutuli, Daniela
AU - Falcone, Marika
PY - 2007/11
Y1 - 2007/11
N2 - Type 1 interferon-β (T1IFN-β) is an innate cytokine and the first-choice therapy for multiple sclerosis (MS). It is still unclear how T1IFN-β, whose main function is to promote innate immunity during infections, plays a beneficial role in autoimmune disease. Here we show that T1IFN-β promoted the expansion and function of invariant natural killer (iNKT) cells, an innate T-cell subset with strong immune regulatory properties that is able to prevent autoimmune disease in pre-clinical models of MS and type 1 diabetes. Specifically, we observed that T1IFN-β treatment significantly increased the percentages of Vα24+ NKT cells in peripheral blood mononuclear cells of MS patients. Furthermore, iNKT cells of T1IFN-β-treated individuals showed a dramatically improved secretion of cytokines (interleukins 4 and 5 and interferon-γ) in response to antigenic stimulation compared to iNKT cells isolated from the same patients before T1IFN-β treatment. The effect of T1IFN-β on iNKT cells was mediated through the modulation of myeloid dendritic cells (DCs). In fact, DCs modulated in vivo or in vitro by T1IFN-β were more efficient antigen-presenting cells for iNKT cells. Such a modulatory effect of T1IFN-β was associated with up-regulation on DCs of key costimulatory molecules for iNKT (i.e. CD80, CD40 and CD1d). Our data identified the iNKT cell/DC pathway as a new target for the immune regulatory effect of T1IFNs in autoimmune diseases and provide a possible mechanism to explain the clinical efficacy of T1IFN-β in MS.
AB - Type 1 interferon-β (T1IFN-β) is an innate cytokine and the first-choice therapy for multiple sclerosis (MS). It is still unclear how T1IFN-β, whose main function is to promote innate immunity during infections, plays a beneficial role in autoimmune disease. Here we show that T1IFN-β promoted the expansion and function of invariant natural killer (iNKT) cells, an innate T-cell subset with strong immune regulatory properties that is able to prevent autoimmune disease in pre-clinical models of MS and type 1 diabetes. Specifically, we observed that T1IFN-β treatment significantly increased the percentages of Vα24+ NKT cells in peripheral blood mononuclear cells of MS patients. Furthermore, iNKT cells of T1IFN-β-treated individuals showed a dramatically improved secretion of cytokines (interleukins 4 and 5 and interferon-γ) in response to antigenic stimulation compared to iNKT cells isolated from the same patients before T1IFN-β treatment. The effect of T1IFN-β on iNKT cells was mediated through the modulation of myeloid dendritic cells (DCs). In fact, DCs modulated in vivo or in vitro by T1IFN-β were more efficient antigen-presenting cells for iNKT cells. Such a modulatory effect of T1IFN-β was associated with up-regulation on DCs of key costimulatory molecules for iNKT (i.e. CD80, CD40 and CD1d). Our data identified the iNKT cell/DC pathway as a new target for the immune regulatory effect of T1IFNs in autoimmune diseases and provide a possible mechanism to explain the clinical efficacy of T1IFN-β in MS.
KW - Autoimmunity
KW - CD1d-restricted natural killer T cells
KW - Cytokines/interferons
KW - Dendritic cells
KW - Human studies
UR - http://www.scopus.com/inward/record.url?scp=35048887983&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=35048887983&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2567.2007.02655.x
DO - 10.1111/j.1365-2567.2007.02655.x
M3 - Article
C2 - 17617156
AN - SCOPUS:35048887983
VL - 122
SP - 409
EP - 417
JO - Immunology
JF - Immunology
SN - 0019-2805
IS - 3
ER -