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Published in:

01-08-2011

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

Authors: Rituparna Das, Jeremy E. Moss, Eve Robinson, Scott Roberts, Rebecca Levy, Yuka Mizue, Lin Leng, Courtney McDonald, Robert E. Tigelaar, Christina A. Herrick, Richard Bucala

Published in: Journal of Clinical Immunology | Issue 4/2011

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.

Hamid Q, Naseer T, Minshall EM, Song YL, Boguniewicz M, Leung DY. In vivo expression of IL-12 and IL-13 in atopic dermatitis. J Allergy Clin Immunol. 1996;98:225–31.PubMedCrossRef

Huang SK, Xiao HQ, Kleine-Tebbe J, Paciotti G, Marsh DG, Lichtenstein LM, et al. IL-13 expression at the sites of allergen challenge in patients with asthma. J Immunol. 1995;155:2688–94.PubMed

Robinson DS, Hamid Q, Ying S, Tsicopoulos A, Barkans J, Bentley AM, et al. Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma. N Engl J Med. 1992;326:298–304.PubMedCrossRef

van Reijsen FC, Bruijnzeel-Koomen CA, Kalthoff FS, Maggi E, Romagnani S, Westland JK, et al. Skin-derived aeroallergen-specific T-cell clones of Th2 phenotype in patients with atopic dermatitis. J Allergy Clin Immunol. 1992;90:184–93.PubMedCrossRef

Robinson D, Hamid Q, Bentley A, Ying S, Kay AB, Durham SR. Activation of CD4+ T cells, increased TH2-type cytokine mRNA expression, and eosinophil recruitment in bronchoalveolar lavage after allergen inhalation challenge in patients with atopic asthma. J Allergy Clin Immunol. 1993;92:313–24.PubMedCrossRef

Hamid Q, Boguniewicz M, Leung DY. Differential in situ cytokine gene expression in acute versus chronic atopic dermatitis. J Clin Invest. 1994;94:870–6.PubMedCrossRef

Brombacher F. The role of interleukin-13 in infectious diseases and allergy. Bioessays. 2000;22:646–56.PubMedCrossRef

Doherty TM, Kastelein R, Menon S, Andrade S, Coffman RL. Modulation of murine macrophage function by IL-13. J Immunol. 1993;151:7151–60.PubMed

Finkelman FD, Katona IM, Urban Jr JF, Holmes J, Ohara J, Tung AS, et al. IL-4 is required to generate and sustain in vivo IgE responses. J Immunol. 1988;141:2335–41.PubMed

10.

Grunig G, Warnock M, Wakil AE, Venkayya R, Brombacher F, Rennick DM, et al. Requirement for IL-13 independently of IL-4 in experimental asthma. Science. 1998;282:2261–3.PubMedCrossRef

11.

McKenzie AN, Culpepper JA, de Waal Malefyt R, Briere F, Punnonen J, Aversa G, et al. Interleukin 13, a T-cell-derived cytokine that regulates human monocyte and B-cell function. Proc Natl Acad Sci U S A. 1993;90:3735–9.PubMedCrossRef

12.

Wills-Karp M, Luyimbazi J, Xu X, Schofield B, Neben TY, Karp CL, et al. Interleukin-13: central mediator of allergic asthma. Science. 1998;282:2258–61.PubMedCrossRef

13.

Zurawski SM, Chomarat P, Djossou O, Bidaud C, McKenzie AN, Miossec P, et al. The primary binding subunit of the human interleukin-4 receptor is also a component of the interleukin-13 receptor. J Biol Chem. 1995;270:13869–78.PubMedCrossRef

14.

Lin JX, Migone TS, Tsang M, Friedmann M, Weatherbee JA, Zhou L, et al. The role of shared receptor motifs and common Stat proteins in the generation of cytokine pleiotropy and redundancy by IL-2, IL-4, IL-7, IL-13, and IL-15. Immunity. 1995;2:331–9.PubMedCrossRef

15.

Smerz-Bertling C, Duschl A. Both interleukin 4 and interleukin 13 induce tyrosine phosphorylation of the 140-kDa subunit of the interleukin 4 receptor. J Biol Chem. 1995;270:966–70.PubMedCrossRef

16.

Swain SL, Weinberg AD, English M, Huston G. IL-4 directs the development of Th2-like helper effectors. J Immunol. 1990;145:3796–806.PubMed

17.

Zurawski G, de Vries JE. Interleukin 13, an interleukin 4-like cytokine that acts on monocytes and B cells, but not on T cells. Immunol Today. 1994;15:19–26.PubMedCrossRef

18.

Herrick CA, MacLeod H, Glusac E, Tigelaar RE, Bottomly K. Th2 responses induced by epicutaneous or inhalational protein exposure are differentially dependent on IL-4. J Clin Invest. 2000;105:765–75.PubMedCrossRef

19.

Herrick CA, Xu L, McKenzie AN, Tigelaar RE, Bottomly K. IL-13 is necessary, not simply sufficient, for epicutaneously induced Th2 responses to soluble protein antigen. J Immunol. 2003;170:2488–95.PubMed

20.

Foster PS, Hogan SP, Ramsay AJ, Matthaei KI, Young IG. Interleukin 5 deficiency abolishes eosinophilia, airways hyperreactivity, and lung damage in a mouse asthma model. J Exp Med. 1996;183:195–201.PubMedCrossRef

21.

Lee JJ, McGarry MP, Farmer SC, Denzler KL, Larson KA, Carrigan PE, et al. Interleukin-5 expression in the lung epithelium of transgenic mice leads to pulmonary changes pathognomonic of asthma. J Exp Med. 1997;185:2143–56.PubMedCrossRef

22.

Resnick MB, Weller PF. Mechanisms of eosinophil recruitment. Am J Respir Cell Mol Biol. 1993;8:349–55.PubMed

23.

Yamaguchi Y, Hayashi Y, Sugama Y, Miura Y, Kasahara T, Kitamura S, et al. Highly purified murine interleukin 5 (IL-5) stimulates eosinophil function and prolongs in vitro survival. IL-5 as an eosinophil chemotactic factor. J Exp Med. 1988;167:1737–42.PubMedCrossRef

24.

Yamaguchi Y, Suda T, Suda J, Eguchi M, Miura Y, Harada N, et al. Purified interleukin 5 supports the terminal differentiation and proliferation of murine eosinophilic precursors. J Exp Med. 1988;167:43–56.PubMedCrossRef

25.

Zheng W, Flavell RA. The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells. Cell. 1997;89:587–96.PubMedCrossRef

26.

Zhu J, Yamane H, Cote-Sierra J, Guo L, Paul WE. GATA-3 promotes Th2 responses through three different mechanisms: induction of Th2 cytokine production, selective growth of Th2 cells and inhibition of Th1 cell-specific factors. Cell Res. 2006;16:3–10.PubMedCrossRef

27.

Chapoval S, Dasgupta P, Dorsey NJ, Keegan AD. Regulation of the T helper cell type 2 (Th2)/T regulatory cell (Treg) balance by IL-4 and STAT6. J Leukoc Biol. 2010;87:1011–8.PubMedCrossRef

28.

Bettelli E, Dastrange M, Oukka M. Foxp3 interacts with nuclear factor of activated T cells and NF-kappa B to repress cytokine gene expression and effector functions of T helper cells. Proc Natl Acad Sci USA. 2005;102:5138–43.PubMedCrossRef

29.

Choi JM, Shin JH, Sohn MH, Harding MJ, Park JH, Tobiasova Z, et al. Cell-permeable Foxp3 protein alleviates autoimmune disease associated with inflammatory bowel disease and allergic airway inflammation. Proc Natl Acad Sci USA. 2010;107:18575–80.PubMedCrossRef

30.

Bloom BR, Bennett B. Mechanism of a reaction in vitro associated with delayed-type hypersensitivity. Science. 1966;153:80–2.PubMedCrossRef

31.

David JR. Delayed hypersensitivity in vitro: its mediation by cell-free substances formed by lymphoid cell-antigen interaction. Proc Natl Acad Sci USA. 1966;56:72–7.PubMedCrossRef

32.

Mitchell RA, Metz CN, Peng T, Bucala R. Sustained mitogen-activated protein kinase (MAPK) and cytoplasmic phospholipase A2 activation by macrophage migration inhibitory factor (MIF). Regulatory role in cell proliferation and glucocorticoid action. J Biol Chem. 1999;274:18100–6.PubMedCrossRef

33.

Roger T, David J, Glauser MP, Calandra T. MIF regulates innate immune responses through modulation of Toll-like receptor 4. Nature. 2001;414:920–4.PubMedCrossRef

34.

Hudson JD, Shoaibi MA, Maestro R, Carnero A, Hannon GJ, Beach DH. A proinflammatory cytokine inhibits p53 tumor suppressor activity. J Exp Med. 1999;190:1375–82.PubMedCrossRef

35.

Mitchell RA, Liao H, Chesney J, Fingerle-Rowson G, Baugh J, David J, et al. Macrophage migration inhibitory factor (MIF) sustains macrophage proinflammatory function by inhibiting p53: regulatory role in the innate immune response. Proc Natl Acad Sci USA. 2002;99:345–50.PubMedCrossRef

36.

Bucala R. MIF re-discovered: pituitary hormone and glucocorticoid-induced regulator of cytokine production. Cytokine Growth Factor Rev. 1996;7:19–24.PubMedCrossRef

37.

Nishihira J. Macrophage migration inhibitory factor (MIF): its essential role in the immune system and cell growth. J Interferon Cytokine Res. 2000;20:751–62.PubMedCrossRef

38.

Bacher M, Metz CN, Calandra T, Mayer K, Chesney J, Lohoff M, et al. An essential regulatory role for macrophage migration inhibitory factor in T-cell activation. Proc Natl Acad Sci USA. 1996;93:7849–54.PubMedCrossRef

39.

Shimizu T, Abe R, Nishihira J, Shibaki A, Watanabe H, Nakayama T, et al. Impaired contact hypersensitivity in macrophage migration inhibitory factor-deficient mice. Eur J Immunol. 2003;33:1478–87.PubMedCrossRef

40.

Bernhagen J, Bacher M, Calandra T, Metz CN, Doty SB, Donnelly T, et al. An essential role for macrophage migration inhibitory factor in the tuberculin delayed-type hypersensitivity reaction. J Exp Med. 1996;183:277–82.PubMedCrossRef

41.

Nakamaru Y, Oridate N, Nishihira J, Takagi D, Furuta Y, Fukuda S. Macrophage migration inhibitory factor (MIF) contributes to the development of allergic rhinitis. Cytokine. 2005;31:103–8.PubMedCrossRef

42.

Mizue Y, Ghani S, Leng L, McDonald C, Kong P, Baugh J, et al. Role for macrophage migration inhibitory factor in asthma. Proc Natl Acad Sci USA. 2005;102:14410–5.PubMedCrossRef

43.

Wang B, Huang X, Wolters PJ, Sun J, Kitamoto S, Yang M, et al. Cutting edge: deficiency of macrophage migration inhibitory factor impairs murine airway allergic responses. J Immunol. 2006;177:5779–84.PubMed

44.

Yoshihisa Y, Makino T, Matsunaga K, Honda A, Norisugi O, Abe R, Shimizu H, and Shimizu T. Macrophage migration inhibitory factor is essential for eosinophil recruitment in allergen-induced skin inflammation. J Invest Dermatol. 2011;131:925–931

45.

Hizawa N, Yamaguchi E, Takahashi D, Nishihira J, Nishimura M. Functional polymorphisms in the promoter region of macrophage migration inhibitory factor and atopy. Am J Respir Crit Care Med. 2004;169:1014–8.PubMedCrossRef

46.

Wu J, Fu S, Ren X, Jin Y, Huang X, Zhang X, et al. Association of MIF promoter polymorphisms with childhood asthma in a northeastern Chinese population. Tissue Antigens. 2009;73:302–6.PubMedCrossRef

47.

Shimizu T, Abe R, Nakamura H, Ohkawara A, Suzuki M, Nishihira J. High expression of macrophage migration inhibitory factor in human melanoma cells and its role in tumor cell growth and angiogenesis. Biochem Biophys Res Commun. 1999;264:751–8.PubMedCrossRef

48.

Shimizu T, Abe R, Ohkawara A, Mizue Y, Nishihira J. Macrophage migration inhibitory factor is an essential immunoregulatory cytokine in atopic dermatitis. Biochem Biophys Res Commun. 1997;240:173–8.PubMedCrossRef

49.

Shimizu T, Abe R, Ohkawara A, Nishihira J. Increased production of macrophage migration inhibitory factor by PBMCs of atopic dermatitis. J Allergy Clin Immunol. 1999;104:659–64.PubMedCrossRef

50.

Rossi AG, Haslett C, Hirani N, Greening AP, Rahman I, Metz CN, et al. Human circulating eosinophils secrete macrophage migration inhibitory factor (MIF). Potential role in asthma. J Clin Invest. 1998;101:2869–74.PubMedCrossRef

51.

Yamaguchi E, Nishihira J, Shimizu T, Takahashi T, Kitashiro N, Hizawa N, et al. Macrophage migration inhibitory factor (MIF) in bronchial asthma. Clin Exp Allergy. 2000;30:1244–9.PubMedCrossRef

52.

Chen PF, Luo YL, Wang W, Wang JX, Lai WY, Hu SM, et al. ISO-1, a macrophage migration inhibitory factor antagonist, inhibits airway remodeling in a murine model of chronic asthma. Mol Med. 2010;16:400–8.PubMedCrossRef

53.

Amano T, Nishihira J, Miki I. Blockade of macrophage migration inhibitory factor (MIF) prevents the antigen-induced response in a murine model of allergic airway inflammation. Inflamm Res. 2007;56:24–31.PubMedCrossRef

54.

Spergel JM, Paller AS. Atopic dermatitis and the atopic march. J Allergy Clin Immunol. 2003;112:S118–27.PubMedCrossRef

55.

Bozza M, Satoskar AR, Lin G, Lu B, Humbles AA, Gerard C, et al. Targeted disruption of migration inhibitory factor gene reveals its critical role in sepsis. J Exp Med. 1999;189:341–6.PubMedCrossRef

56.

Shachar I, Flavell RA. Requirement for invariant chain in B cell maturation and function. Science. 1996;274:106–8.PubMedCrossRef

57.

Koni PA, Flavell RA. Lymph node germinal centers form in the absence of follicular dendritic cell networks. J Exp Med. 1999;189:855–64.PubMedCrossRef

58.

Levin D, Constant S, Pasqualini T, Flavell R, Bottomly K. Role of dendritic cells in the priming of CD4+ T lymphocytes to peptide antigen in vivo. J Immunol. 1993;151:6742–50.PubMed

59.

Alexopoulou L, Holt AC, Medzhitov R, Flavell RA. Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature. 2001;413:732–8.PubMedCrossRef

60.

Click RE, Benck L, Alter BJ. Immune responses in vitro. I. Culture conditions for antibody synthesis. Cell Immunol. 1972;3:264–76.PubMedCrossRef

61.

Mukherjee S, Ahmed A, Malu S, Nandi D. Modulation of cell cycle progression by CTLA4-CD80/CD86 interactions on CD4+ T cells depends on strength of the CD3 signal: critical role for IL-2. J Leukoc Biol. 2006;80:66–74.PubMedCrossRef

62.

Leng L, Metz CN, Fang Y, Xu J, Donnelly S, Baugh J, et al. MIF signal transduction initiated by binding to CD74. J Exp Med. 2003;197:1467–76.PubMedCrossRef

63.

Shi X, Leng L, Wang T, Wang W, Du X, Li J, et al. CD44 is the signaling component of the macrophage migration inhibitory factor–CD74 receptor complex. Immunity. 2006;25:595–606.PubMedCrossRef

64.

Topilski I, Harmelin A, Flavell RA, Levo Y, Shachar I. Preferential Th1 immune response in invariant chain-deficient mice. J Immunol. 2002;168:1610–7.PubMed

65.

Coleman AM, Rendon BE, Zhao M, Qian MW, Bucala R, Xin D, et al. Cooperative regulation of non-small cell lung carcinoma angiogenic potential by macrophage migration inhibitory factor and its homolog, D-dopachrome tautomerase. J Immunol. 2008;181:2330–7.PubMed

66.

Cohn L, Homer RJ, Marinov A, Rankin J, Bottomly K. Induction of airway mucus production By T helper 2 (Th2) cells: a critical role for interleukin 4 in cell recruitment but not mucus production. J Exp Med. 1997;186:1737–47.PubMedCrossRef

67.

Spergel JM. From atopic dermatitis to asthma: the atopic march. Ann Allergy Asthma Immunol. 2010;105:99–106; quiz 107–109, 117

68.

Calandra T, Bernhagen J, Metz CN, Spiegel LA, Bacher M, Donnelly T, et al. MIF as a glucocorticoid-induced modulator of cytokine production. Nature. 1995;377:68–71.PubMedCrossRef

69.

Akei HS, Brandt EB, Mishra A, Strait RT, Finkelman FD, Warrier MR, et al. Epicutaneous aeroallergen exposure induces systemic TH2 immunity that predisposes to allergic nasal responses. J Allergy Clin Immunol. 2006;118:62–9.PubMedCrossRef

70.

Jin H, Kumar L, Mathias C, Zurakowski D, Oettgen H, Gorelik L, et al. Toll-like receptor 2 is important for the T(H)1 response to cutaneous sensitization. J Allergy Clin Immunol. 2009;123:875–82. e871.PubMedCrossRef

71.

Fingerle-Rowson G, Petrenko O, Metz CN, Forsthuber TG, Mitchell R, Huss R, et al. The p53-dependent effects of macrophage migration inhibitory factor revealed by gene targeting. Proc Natl Acad Sci USA. 2003;100:9354–9.PubMedCrossRef

72.

Xie L, Qiao X, Wu Y, Tang J. β-Arrestin1 mediates the endocytosis and functions of macrophage migration inhibitory factor. PLoS One. 2011;6(1):e16428.PubMedCrossRef

73.

Lue H, Dewor M, Leng L, Bucala R, Bernhagen J. Activation of the JNK signalling pathway by macrophage migration inhibitory factor (MIF) and dependence on CXCR4 and CD74. Cell Signal. 2010;23:135–44.PubMedCrossRef

74.

Flaster H, Bernhagen J, Calandra T, Bucala R. The macrophage migration inhibitory factor-glucocorticoid dyad: regulation of inflammation and immunity. Mol Endocrinol. 2007;21:1267–80.PubMedCrossRef

75.

Hoi AY, Hickey MJ, Hall P, Yamana J, O’Sullivan KM, Santos LL, et al. Macrophage migration inhibitory factor deficiency attenuates macrophage recruitment, glomerulonephritis, and lethality in MRL/lpr mice. J Immunol. 2006;177:5687–96.PubMed

76.

Park SK, Cho MK, Park HK, Lee KH, Lee SJ, Choi SH, et al. Macrophage migration inhibitory factor homologs of Anisakis simplex suppress Th2 response in allergic airway inflammation model via CD4+CD25+Foxp3+ T cell recruitment. J Immunol. 2009;182:6907–14.PubMedCrossRef

77.

Lolis E, Bucala R. Therapeutic approaches to innate immunity: severe sepsis and septic shock. Nat Rev Drug Discov. 2003;2:635–45.PubMedCrossRef

Title: Role of Macrophage Migration Inhibitory Factor in the Th2 Immune Response to Epicutaneous Sensitization
Authors: Rituparna Das
Jeremy E. Moss
Eve Robinson
Scott Roberts
Rebecca Levy
Yuka Mizue
Lin Leng
Courtney McDonald
Robert E. Tigelaar
Christina A. Herrick
Richard Bucala
Publication date: 01-08-2011
Publisher: Springer US
Published in: Journal of Clinical Immunology / Issue 4/2011
Print ISSN: 0271-9142
Electronic ISSN: 1573-2592
DOI: https://doi.org/10.1007/s10875-011-9541-7

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