Endogenous galectin-1 fine-tunes the tolerogenic function of dendritic cells

ILARREGUI JM; CROCI DO; SALATINO M; TOSCANO MA; VERMEULEN ME; GEFFNER JR; RABINOVICH GA

Viña del Mar, Chile

Congreso; ALAI 2009- Latinoamerican Congress of Immunology, Viña del Mar Chile; 2009

Soc. Latinoamericana de Inmunología

&amp;amp;amp;amp;amp;amp;lt;!-- /* Font Definitions */ @font-face {font-family:"Cambria Math"; panose-1:2 4 5 3 5 4 6 3 2 4; mso-font-charset:0; mso-generic-font-family:roman; mso-font-pitch:variable; mso-font-signature:-1610611985 1107304683 0 0 159 0;} @font-face {font-family:Calibri; panose-1:2 15 5 2 2 2 4 3 2 4; mso-font-charset:0; mso-generic-font-family:swiss; mso-font-pitch:variable; mso-font-signature:-1610611985 1073750139 0 0 159 0;} /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-unhide:no; mso-style-qformat:yes; mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman","serif"; mso-fareast-font-family:Calibri; mso-ansi-language:ES; mso-fareast-language:ES;} .MsoChpDefault {mso-style-type:export-only; mso-default-props:yes; font-size:10.0pt; mso-ansi-font-size:10.0pt; mso-bidi-font-size:10.0pt; mso-ascii-font-family:Century; mso-fareast-font-family:Calibri; mso-hansi-font-family:Century;} @page Section1 {size:21.0cm 842.0pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:35.45pt; mso-footer-margin:35.45pt; mso-paper-source:0;} div.Section1 {page:Section1;} --&amp;amp;amp;amp;amp;amp;gt; Galectin-1, a glycan-binding protein, plays a critical role as a regulator of immune cell homeostasis. Here, we examined the role of endogenous galectin-1 in the regulation of autoimmune inflammation and the physiology of murine dendritic cells (DCs). We found a progressive increase in galectin-1 expression in lymph nodes from animals with MOG35-55- induced experimental autoimmune encephalomyelitis (EAE), which correlated with the pace of the clinical disease (p<0.05). A similar expression profile was observed in CD11c+ DCs purified from spleens at different times of EAE induction (p<0.05). Notably, DCs lacking galectin-1 (Lgals1-/-) had greater immunogenic potential in in vitro and in vivo settings(p<0.05). Consistent with its regulatory function, galectin-1-sufficient DCs isolated from spleens at day 21 of EAE (peak of the disease) and adoptively transferred into Lgals1-/- mice at the day of disease onset successfully restored T-cell tolerance and contributed to the resolution of autoimmune inflammation as reflected by reduced clinical severity, diminished IL-17 and IFN-g production and augmented IL-10 secretion by lymph node cells from Lgals1-/- mice receiving wild-type DCs, compared to Lgals1-/- mice receiving DCs devoid of this protein. We conclude that galectin-1 plays a critical role in limiting the inflammatory response and in fine-tuning the immunogenic function of DCs, thus contributing to disease recovery.