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Role of Macrophage Migration Inhibitory Factor in the Th2 Immune Response to Epicutaneous Sensitization

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Abstract

We examined the role of macrophage migration inhibitory factor (MIF) in the generation of the Th2 response using MIF-deficient mice in a model of epicutaneous sensitization to ovalbumin. Lymph node cells from sensitized MIF-deficient mice produce lower levels of Th2 cytokines after antigen challenge when compared to their wild-type counterparts. Sensitized mice lacking MIF show less pulmonary inflammation after intranasal antigen exposure. Mice deficient in CD74, the MIF receptor, also are unable to generate an inflammatory response to epicutaneous sensitization. Examination of the elicitation phase of the atopic response using DO11.10 OVA TCR transgenic animals shows that T cell proliferation and IL-2 production are strongly impaired in MIF-deficient T cells. This defect is most profound when both T cells and antigen-presenting cells are lacking MIF. These data suggest that MIF is crucial both for the sensitization and the elicitation phases of a Th2-type immune response in allergic disease.

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Abbreviations

AD:

Atopic dermatitis

APCs:

Antigen-presenting cells

BAL:

Bronchoalveolar lavage

EC:

Epicutaneous

ERK 1/2:

Extracellular signal-regulated kinase

IFN-γ:

Interferon-gamma

IL:

Interleukin

IN:

Intranasal

IP:

Intraperitoneal

LN:

Lymph node

MHC:

Major histocompatibility complex

MIF:

Macrophage migration inhibitory factor

TCR:

T cell receptor

TNCB:

Trinitrochlorobenzene

TLR:

Toll-like receptor

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Acknowledgments

We thank Jason Griffith for providing thoughtful discussions and insights, and Idit Shachar of the Weizmann Institute, Rehovot, Israel, for providing the BALB/c CD74-KO mice. We also acknowledge the following grant support: RD NIH grant 2 T32 AR 007107-36 and Yale-New Haven Hospital William Wirt Winchester Grant, RB NIH grants AR050498 and AR049610, CH NIH grant AI069396, and NIH Grant T30-AR07016, Dermatology Foundation.

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Authors and Affiliations

  1. Department of Medicine, Yale University School of Medicine, The Anlyan Center Room S525, 300 Cedar Street, New Haven, CT, 06520-8031, USA

    Rituparna Das, Scott Roberts, Rebecca Levy, Yuka Mizue, Lin Leng, Courtney McDonald & Richard Bucala

  2. Department of Dermatology, Yale University School of Medicine, New Haven, CT, 06520, USA

    Jeremy E. Moss, Eve Robinson, Robert E. Tigelaar & Christina A. Herrick

  3. Department of Immunobiology, Yale University School of Medicine, New Haven, CT, 06520, USA

    Eve Robinson, Robert E. Tigelaar & Christina A. Herrick

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  1. Rituparna Das
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  2. Jeremy E. Moss
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  3. Eve Robinson
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  4. Scott Roberts
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  5. Rebecca Levy
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  7. Lin Leng
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  9. Robert E. Tigelaar
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  10. Christina A. Herrick
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  11. Richard Bucala
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Correspondence to Richard Bucala.

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Das, R., Moss, J.E., Robinson, E. et al. Role of Macrophage Migration Inhibitory Factor in the Th2 Immune Response to Epicutaneous Sensitization. J Clin Immunol 31, 666–680 (2011). https://doi.org/10.1007/s10875-011-9541-7

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