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Journal of Diabetes Research
Volume 2016 (2016), Article ID 7053963, 19 pages
Research Article

Altered Macrophage and Dendritic Cell Response in Mif−/− Mice Reveals a Role of Mif for Inflammatory-Th1 Response in Type 1 Diabetes

1Unidad de Biomedicina, Facultad de Estudios Superiores (FES) Iztacala, Universidad Nacional Autónoma de México (UNAM), 54090 Tlalnepantla, MEX, Mexico
2Carrera de Optometría, FES-Iztacala, UNAM, 54090 Tlalnepantla, MEX, Mexico
3Departamento de Neurodesarrollo y Fisiología, Instituto de Fisiología Celular, UNAM, 04510 Coyoacán, MEX, Mexico

Received 31 May 2016; Accepted 10 July 2016

Academic Editor: Jixin Zhong

Copyright © 2016 Yuriko Itzel Sánchez-Zamora et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Macrophage migration inhibitory factor (Mif) is highly expressed in type 1 diabetes mellitus (T1DM). However, there is limited information about how Mif influences the activation of macrophages (Mφ) and dendritic cells (DC) in T1DM. To address this issue, we induced T1DM by administering multiple low doses of streptozotocin (STZ) to Mif−/− or wild-type (Wt) BALB/c mice. We found that Mif−/− mice treated with STZ (Mif−/−STZ) developed lower levels of hyperglycemia, inflammatory cytokines, and specific pancreatic islet antigen- (PIAg-) IgG and displayed reduced cellular infiltration into the pancreatic islets compared to Wt mice treated with STZ (WtSTZ). Moreover, Mφ and DC from Mif−/−STZ displayed lower expression of MHC-II, costimulatory molecules CD80, CD86, and CD40, Toll-like receptor- (TLR-) 2, and TLR-4 than WtSTZ. These changes were associated with a reduced capacity of Mφ and DC from Mif−/−STZ to induce proliferation in ovalbumin-specific T cells. All the deficiencies observed in Mif−/−STZ were recovered by exogenous administration of recombinant Mif. These findings suggest that Mif plays a role in the molecular mechanisms of Mφ and DC activation and drives T cell responses involved in the pathology of T1DM. Therefore, Mif is a potential therapeutic target to reduce the pathology of T1DM.