| First Author | Kim HK | Year | 2019 |
| Journal | FASEB J | Volume | 33 |
| Issue | 6 | Pages | 6919-6932 |
| PubMed ID | 30817226 | Mgi Jnum | J:292592 |
| Mgi Id | MGI:6447203 | Doi | 10.1096/fj.201802433R |
| Citation | Kim HK, et al. (2019) Macrophage migration inhibitory factor regulates innate gammadelta T-cell responses via IL-17 expression. FASEB J 33(6):6919-6932 |
| abstractText | T cells expressing invariant gammadelta antigen receptors (gammadelta T cells) bridge innate and adaptive immunity and facilitate barrier responses to pathogens. Macrophage migration inhibitory factor (MIF) is an upstream mediator of host defense that up-regulates the expression of pattern recognition receptors and sustains inflammatory responses by inhibiting activation-induced apoptosis in monocytes and macrophages. Surprisingly, Mif(-/-) gammadelta T cells, when compared with wild type, were observed to produce >10-fold higher levels of the proinflammatory cytokine IL-17 after stimulation with gram-positive exotoxins. High-IL-17 expression was associated with the characteristic features of IL-17-producing gammadelta T (gammadelta17) cells, including expression of IL-23R, IL-1R1, and the transcription factors RORgammat and Sox13. In the gram-positive model of shock mediated by toxic shock syndrome toxin (TSST-1), Mif(-/-) mice succumbed to death more quickly with increased pulmonary neutrophil accumulation and higher production of cytokines, including IL-1beta and IL-23. Mif(-/-) gammadelta T cells also produced high levels of IL-17 in response to Mycobacterium lipomannan, and depletion of gammadelta T cells improved survival from acutely lethal Mycobacterium infection or TSST-1 administration. These data indicate that MIF deficiency is associated with a compensatory amplification of gammadelta17 cell responses, with implications for innate immunity and IL-17-mediated pathology in situations such as gram-positive toxic shock or Mycobacterium infection.-Kim, H. K., Garcia, A. B., Siu, E., Tilstam, P., Das, R., Roberts, S., Leng, L., Bucala, R. Macrophage migration inhibitory factor regulates innate gammadelta T-cell responses via IL-17 expression. |
