Mast cells (MCs) are best known as key immune players in immunoglobulin E (IgE)-dependent allergic reactions. In recent years, several lines of evidence have suggested that MCs might play an important role in several pathological conditions, including autoimmune disorders such as multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), an animal model for MS. Since their first description in MS plaques in the late 1800s, much effort has been put into elucidating the contribution of MCs to the development of central nervous system (CNS) autoimmunity. Mouse models of MC-deficiency have provided a valuable experimental tool for dissecting MC involvement in MS and EAE. However, to date there is still major controversy concerning the function of MCs in these diseases. Indeed, although MCs have been classically proposed as having a detrimental and pro-inflammatory role, recent literature has questioned and resized the contribution of MCs to the pathology of MS and EAE. In this review, we will present the main evidence obtained in MS and EAE on this topic, and discuss the critical and controversial aspects of such evidence.
References
[1]
Noseworthy, J.H.; Lucchinetti, C.; Rodriguez, M.; Weinshenker, B.G. Multiple sclerosis. N. Engl. J. Med 2000, 343, 938–952.
[2]
Steinman, L. Multiple sclerosis: A two-stage disease. Nat. Immunol 2001, 2, 762–764.
[3]
Compston, A.; Coles, A. Multiple sclerosis. Lancet 2002, 359, 1221–1231.
[4]
Hauser, S.L.; Oksenberg, J.R. The neurobiology of multiple sclerosis: Genes, inflammation, and neurodegeneration. Neuron 2006, 52, 61–76.
[5]
Voskuhl, R.R.; Gold, S.M. Sex-related factors in multiple sclerosis susceptibility and progression. Nat. Rev. Neurol 2012, 8, 255–263.
[6]
Goverman, J. Autoimmune T cell responses in the central nervous system. Nat. Rev. Immunol 2009, 9, 393–407.
Lafaille, J.J.; Keere, F.V.; Hsu, A.L.; Baron, J.L.; Haas, W.; Raine, C.S.; Tonegawa, S. Myelin basic protein-specific T helper 2 (Th2) cells cause experimental autoimmune encephalomyelitis in immunodeficient hosts rather than protect them from the disease. J. Exp. Med 1997, 186, 307–312.
[9]
Pedotti, R.; DeVoss, J.J.; Youssef, S.; Mitchell, D.; Wedemeyer, J.; Madanat, R.; Garren, H.; Fontoura, P.; Tsai, M.; Galli, S.J.; et al. Multiple elements of the allergic arm of the immune response modulate autoimmune demyelination. Proc. Natl. Acad. Sci. USA 2003, 100, 1867–1872.
[10]
Pedotti, R.; De voss, J.J.; Steinman, L.; Galli, S.J. Involvement of both ‘allergic’ and ‘autoimmune’mechanisms in EAE, MS and other autoimmune diseases. Trends Immunol 2003, 24, 479–484.
[11]
Zappulla, J.P.; Arock, M.; Mars, L.T.; Liblau, R.S. Mast cells: New targets for multiple sclerosis therapy? J. Neuroimmunol 2002, 131, 5–20.
[12]
Olsson, Y. Mast cells in plaques of multiple sclerosis. Acta Neurol. Scand 1974, 50, 611–618.
[13]
Theoharides, T.C. Mast cells: The immune gate to the brain. Life Sci 1990, 46, 607–617.
[14]
Ibrahim, M.Z.; Reder, A.T.; Lawand, R.; Takash, W.; Sallouh-Khatib, S. The mast cells of the multiple sclerosis brain. J. Neuroimmunol 1996, 70, 131–138.
[15]
Bartholomaus, I.; Kawakami, N.; Odoardi, F.; Schlager, C.; Miljkovic, D.; Ellwart, J.W.; Klinkert, W.E.; Flugel-Koch, C.; Issekutz, T.B.; Wekerle, H.; et al. Effector T cell interactions with meningeal vascular structures in nascent autoimmune CNS lesions. Nature 2009, 462, 94–98.
[16]
Tanzola, M.B.; Robbie-Ryan, M.; Gutekunst, C.A.; Brown, M.A. Mast cells exert effects outside the central nervous system to influence experimental allergic encephalomyelitis disease course. J. Immunol 2003, 171, 4385–4391.
[17]
Gregory, G.D.; Robbie-Ryan, M.; Secor, V.H.; Sabatino, J.J., Jr; Brown, M.A. Mast cells are required for optimal autoreactive T cell responses in a murine model of multiple sclerosis. Eur J. Immunol. 2005, 35, 3478–3486.
[18]
Galli, S.J.; Borregaard, N.; Wynn, T.A. Phenotypic and functional plasticity of cells of innate immunity: Macrophages, mast cells and neutrophils. Nat. Immunol 2011, 12, 1035–1044.
[19]
Chen, C.C.; Grimbaldeston, M.A.; Tsai, M.; Weissman, I.L.; Galli, S.J. Identification of mast cell progenitors in adult mice. Proc. Natl. Acad. Sci. USA 2005, 102, 11408–11413.
[20]
Galli, S.J.; Kalesnikoff, J.; Grimbaldeston, M.A.; Piliponsky, A.M.; Williams, C.M.; Tsai, M. Mast cells as “tunable” effector and immunoregulatory cells: Recent advances. Annu Rev. Immunol 2005, 23, 749–786.
[21]
Bischoff, S.C. Role of mast cells in allergic and non-allergic immune responses: Comparison of human and murine data. Nat. Rev. Immunol 2007, 7, 93–104.
[22]
Dudeck, A.; Dudeck, J.; Scholten, J.; Petzold, A.; Surianarayanan, S.; Kohler, A.; Peschke, K.; Vohringer, D.; Waskow, C.; Krieg, T.; et al. Mast cells are key promoters of contact allergy that mediate the adjuvant effects of haptens. Immunity 2011, 34, 973–984.
[23]
Kunder, C.A.; St John, A.L.; Li, G.; Leong, K.W.; Berwin, B.; Staats, H.F.; Abraham, S.N. Mast cell-derived particles deliver peripheral signals to remote lymph nodes. J. Exp. Med 2009, 206, 2455–2467.
[24]
Byrne, S.N.; Limon-Flores, A.Y.; Ullrich, S.E. Mast cell migration from the skin to the draining lymph nodes upon ultraviolet irradiation represents a key step in the induction of immune suppression. J. Immunol 2008, 180, 4648–4655.
[25]
Kitamura, Y. Heterogeneity of mast cells and phenotypic change between subpopulations. Annu. Rev. Immunol 1989, 7, 59–76.
[26]
Galli, S.J.; Nakae, S.; Tsai, M. Mast cells in the development of adaptive immune responses. Nat. Immunol 2005, 6, 135–142.
[27]
Sonoda, S.; Sonoda, T.; Nakano, T.; Kanayama, Y.; Kanakura, Y.; Asai, H.; Yonezawa, T.; Kitamura, Y. Development of mucosal mast cells after injection of a single connective tissue-type mast cell in the stomach mucosa of genetically mast cell-deficient W/Wv mice. J. Immunol 1986, 137, 1319–1322.
[28]
Gilfillan, A.M.; Tkaczyk, C. Integrated signalling pathways for mast-cell activation. Nat. Rev. Immunol 2006, 6, 218–230.
[29]
Galli, S.J.; Tsai, M.; Piliponsky, A.M. The development of allergic inflammation. Nature 2008, 454, 445–454.
[30]
Wasiuk, A.; de Vries, V.C.; Hartmann, K.; Roers, A.; Noelle, R.J. Mast cells as regulators of adaptive immunity to tumours. Clin. Exp. Immunol 2009, 155, 140–146.
[31]
Kalesnikoff, J.; Huber, M.; Lam, V.; Damen, J.E.; Zhang, J.; Siraganian, R.P.; Krystal, G. Monomeric IgE stimulates signaling pathways in mast cells that lead to cytokine production and cell survival. Immunity 2001, 14, 801–811.
[32]
Miyajima, I.; Dombrowicz, D.; Martin, T.R.; Ravetch, J.V.; Kinet, J.P.; Galli, S.J. Systemic anaphylaxis in the mouse can be mediated largely through IgG1 and Fc gammaRIII. Assessment of the cardiopulmonary changes, mast cell degranulation, and death associated with active or IgE- or IgG1-dependent passive anaphylaxis. J. Clin. Invest 1997, 99, 901–914.
[33]
Finkelman, F.D.; Rothenberg, M.E.; Brandt, E.B.; Morris, S.C.; Strait, R.T. Molecular mechanisms of anaphylaxis: Lessons from studies with murine models. J. Allergy Clin. Immunol. 2005, 115, 449–457. quiz 458.
[34]
Brenner, T.; Soffer, D.; Shalit, M.; Levi-Schaffer, F. Mast cells in experimental allergic encephalomyelitis: Characterization, distribution in the CNS and in vitro activation by myelin basic protein and neuropeptides. J. Neurol. Sci 1994, 122, 210–213.
[35]
Medic, N.; Vita, F.; Abbate, R.; Soranzo, M.R.; Pacor, S.; Fabbretti, E.; Borelli, V.; Zabucchi, G. Mast cell activation by myelin through scavenger receptor. J. Neuroimmunol 2008, 200, 27–40.
[36]
Skaper, S.D.; Facci, L.; Romanello, S.; Leon, A. Mast cell activation causes delayed neurodegeneration in mixed hippocampal cultures via the nitric oxide pathway. J. Neurochem 1996, 66, 1157–1166.
[37]
Levi-Montalcini, R.; Skaper, S.D.; Dal Toso, R.; Petrelli, L.; Leon, A. Nerve growth factor: From neurotrophin to neurokine. Trends Neurosci 1996, 19, 514–520.
[38]
Leal-Berumen, I.; Conlon, P.; Marshall, J.S. IL-6 production by rat peritoneal mast cells is not necessarily preceded by histamine release and can be induced by bacterial lipopolysaccharide. J. Immunol 1994, 152, 5468–5476.
[39]
Mrabet-Dahbi, S.; Metz, M.; Dudeck, A.; Zuberbier, T.; Maurer, M. Murine mast cells secrete a unique profile of cytokines and prostaglandins in response to distinct TLR2 ligands. Exp. Dermatol 2009, 18, 437–444.
[40]
Leon, A.; Buriani, A.; Dal Toso, R.; Fabris, M.; Romanello, S.; Aloe, L.; Levi-Montalcini, R. Mast cells synthesize, store, and release nerve growth factor. Proc. Natl. Acad. Sci. USA 1994, 91, 3739–3743.
[41]
Horigome, K.; Pryor, J.C.; Bullock, E.D.; Johnson, E.M., Jr. Mediator release from mast cells by nerve growth factor. Neurotrophin specificity and receptor mediation. J. Biol. Chem. 1993, 268, 14881–14887.
[42]
Laudiero, L.B.; Aloe, L.; Levi-Montalcini, R.; Buttinelli, C.; Schilter, D.; Gillessen, S.; Otten, U. Multiple sclerosis patients express increased levels of beta-nerve growth factor in cerebrospinal fluid. Neurosci. Lett 1992, 147, 9–12.
[43]
Shevach, E.M. Mechanisms of foxp3+ T regulatory cell-mediated suppression. Immunity 2009, 30, 636–645.
[44]
Lu, L.F.; Lind, E.F.; Gondek, D.C.; Bennett, K.A.; Gleeson, M.W.; Pino-Lagos, K.; Scott, Z.A.; Coyle, A.J.; Reed, J.L.; Van Snick, J.; et al. Mast cells are essential intermediaries in regulatory T-cell tolerance. Nature 2006, 442, 997–1002.
Forward, N.A.; Furlong, S.J.; Yang, Y.; Lin, T.J.; Hoskin, D.W. Mast cells down-regulate CD4+CD25+ T regulatory cell suppressor function via histamine H1 receptor interaction. J. Immunol 2009, 183, 3014–3022.
[49]
Gri, G.; Piconese, S.; Frossi, B.; Manfroi, V.; Merluzzi, S.; Tripodo, C.; Viola, A.; Odom, S.; Rivera, J.; Colombo, M.P.; et al. CD4+CD25+ regulatory T cells suppress mast cell degranulation and allergic responses through OX40-OX40L interaction. Immunity 2008, 29, 771–781.
[50]
Chen, R.; Ning, G.; Zhao, M.L.; Fleming, M.G.; Diaz, L.A.; Werb, Z.; Liu, Z. Mast cells play a key role in neutrophil recruitment in experimental bullous pemphigoid. J. Clin. Invest 2001, 108, 1151–1158.
[51]
Lin, L.; Gerth, A.J.; Peng, S.L. Susceptibility of mast cell-deficient W/Wv mice to pristane-induced experimental lupus nephritis. Immunol. Lett 2004, 91, 93–97.
[52]
Hochegger, K.; Siebenhaar, F.; Vielhauer, V.; Heininger, D.; Mayadas, T.N.; Mayer, G.; Maurer, M.; Rosenkranz, A.R. Role of mast cells in experimental anti-glomerular basement membrane glomerulonephritis. Eur. J. Immunol 2005, 35, 3074–3082.
[53]
Kanamaru, Y.; Scandiuzzi, L.; Essig, M.; Brochetta, C.; Guerin-Marchand, C.; Tomino, Y.; Monteiro, R.C.; Peuchmaur, M.; Blank, U. Mast cell-mediated remodeling and fibrinolytic activity protect against fatal glomerulonephritis. J. Immunol 2006, 176, 5607–5615.
[54]
Lee, D.M.; Friend, D.S.; Gurish, M.F.; Benoist, C.; Mathis, D.; Brenner, M.B. Mast cells: A cellular link between autoantibodies and inflammatory arthritis. Science 2002, 297, 1689–1692.
[55]
Nigrovic, P.A.; Binstadt, B.A.; Monach, P.A.; Johnsen, A.; Gurish, M.; Iwakura, Y.; Benoist, C.; Mathis, D.; Lee, D.M. Mast cells contribute to initiation of autoantibody-mediated arthritis via IL-1. Proc. Natl. Acad. Sci. USA 2007, 104, 2325–2330.
[56]
Zhou, J.S.; Xing, W.; Friend, D.S.; Austen, K.F.; Katz, H.R. Mast cell deficiency in Kit (W-sh) mice does not impair antibody-mediated arthritis. J. Exp. Med 2007, 204, 2797–2802.
[57]
Feyerabend, T.B.; Weiser, A.; Tietz, A.; Stassen, M.; Harris, N.; Kopf, M.; Radermacher, P.; Moller, P.; Benoist, C.; Mathis, D.; et al. Cre-mediated cell ablation contests mast cell contribution in models of antibody- and T cell-mediated autoimmunity. Immunity 2011, 35, 832–844.
[58]
Kruger, P.G.; Bo, L.; Myhr, K.M.; Karlsen, A.E.; Taule, A.; Nyland, H.I.; Mork, S. Mast cells and multiple sclerosis: A light and electron microscopic study of mast cells in multiple sclerosis emphasizing staining procedures. Acta Neurol. Scand 1990, 81, 31–36.
[59]
Toms, R.; Weiner, H.L.; Johnson, D. Identification of IgE-positive cells and mast cells in frozen sections of multiple sclerosis brains. J. Neuroimmunol 1990, 30, 169–177.
[60]
Kruger, P.G. Mast cells and multiple sclerosis: A quantitative analysis. Neuropathol. Appl. Neurobiol 2001, 27, 275–280.
[61]
Couturier, N.; Zappulla, J.P.; Lauwers-Cances, V.; Uro-Coste, E.; Delisle, M.B.; Clanet, M.; Montagne, L.; van der Valk, P.; Bo, L.; Liblau, R.S. Mast cell transcripts are increased within and outside multiple sclerosis lesions. J. Neuroimmunol 2008, 195, 176–185.
[62]
Lock, C.; Hermans, G.; Pedotti, R.; Brendolan, A.; Schadt, E.; Garren, H.; Langer-Gould, A.; Strober, S.; Cannella, B.; Allard, J.; et al. Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis. Nat. Med 2002, 8, 500–508.
[63]
Rozniecki, J.J.; Hauser, S.L.; Stein, M.; Lincoln, R.; Theoharides, T.C. Elevated mast cell tryptase in cerebrospinal fluid of multiple sclerosis patients. Ann. Neurol 1995, 37, 63–66.
[64]
Steinman, L.; Zamvil, S.S. Virtues and pitfalls of EAE for the development of therapies for multiple sclerosis. Trends Immunol 2005, 26, 565–571.
[65]
Baxter, A.G. The origin and application of experimental autoimmune encephalomyelitis. Nat. Rev. Immunol 2007, 7, 904–912.
[66]
Kabat, E.A.; Wolf, A.; Bezer, A.E. The rapid production of acute disseminated encephalomyelitis in rhesus monkeys by injection of heterologous and homologous brain tissue with adjuvants. J. Exp. Med 1947, 85, 117–130.
[67]
Stromnes, I.M.; Goverman, J.M. Active induction of experimental allergic encephalomyelitis. Nat. Protocol 2006, 1, 1810–1819.
[68]
Mendel, I.; Kerlero de Rosbo, N.; Ben-Nun, A. A myelin oligodendrocyte glycoprotein peptide induces typical chronic experimental autoimmune encephalomyelitis in H-2b mice: Fine specificity and T cell receptor V beta expression of encephalitogenic T cells. Eur. J. Immunol 1995, 25, 1951–1959.
[69]
McRae, B.L.; Kennedy, M.K.; Tan, L.J.; Dal Canto, M.C.; Picha, K.S.; Miller, S.D. Induction of active and adoptive relapsing experimental autoimmune encephalomyelitis (EAE) using an encephalitogenic epitope of proteolipid protein. J. Neuroimmunol 1992, 38, 229–240.
[70]
Zamvil, S.S.; Steinman, L. Diverse targets for intervention during inflammatory and neurodegenerative phases of multiple sclerosis. Neuron 2003, 38, 685–688.
[71]
Miller, S.D.; Karpus, W.J. Experimental autoimmune encephalomyelitis in the mouse. Curr. Protoc. Immunol. 2007, doi:10.1002/0471142735.im1501s88.
[72]
Stanley, N.C.; Jackson, F.L.; Orr, E.L. Attenuation of experimental autoimmune encephalomyelitis by Compound 48/80 in Lewis rats. J. Neuroimmunol 1990, 29, 223–228.
Bo, L.; Olsson, T.; Nyland, H.; Kruger, P.G.; Taule, A.; Mork, S. Mast cells in brains during experimental allergic encephalomyelitis in Lewis rats. J. Neurol. Sci 1991, 105, 135–142.
Orr, E.L. Presence and distribution of nervous system-associated mast cells that may modulate experimental autoimmune encephalomyelitis. Ann. N.Y. Acad. Sci 1988, 540, 723–726.
[77]
Secor, V.H.; Secor, W.E.; Gutekunst, C.A.; Brown, M.A. Mast cells are essential for early onset and severe disease in a murine model of multiple sclerosis. J. Exp. Med 2000, 191, 813–822.
Letourneau, R.; Rozniecki, J.J.; Dimitriadou, V.; Theoharides, T.C. Ultrastructural evidence of brain mast cell activation without degranulation in monkey experimental allergic encephalomyelitis. J. Neuroimmunol 2003, 145, 18–26.
[80]
Dietsch, G.N.; Hinrichs, D.J. The role of mast cells in the elicitation of experimental allergic encephalomyelitis. J. Immunol 1989, 142, 1476–1481.
[81]
Storms, W.; Kaliner, M.A. Cromolyn sodium: Fitting an old friend into current asthma treatment. J. Asthma 2005, 42, 79–89.
[82]
Palomaki, V.A.; Laitinen, J.T. The basic secretagogue compound 48/80 activates G proteins indirectly via stimulation of phospholipase D-lysophosphatidic acid receptor axis and 5-HT1A receptors in rat brain sections. Br. J. Pharmacol 2006, 147, 596–606.
[83]
Galli, S.J.; Grimbaldeston, M.; Tsai, M. Immunomodulatory mast cells: Negative, as well as positive, regulators of immunity. Nat. Rev. Immunol 2008, 8, 478–486.
[84]
Kawakami, T. A crucial door to the mast cell mystery knocked in. J. Immunol 2009, 183, 6861–6862.
[85]
Hayashi, S.; Kunisada, T.; Ogawa, M.; Yamaguchi, K.; Nishikawa, S. Exon skipping by mutation of an authentic splice site of c-kit gene in W/W mouse. Nucleic Acids Res 1991, 19, 1267–1271.
[86]
Nocka, K.; Tan, J.C.; Chiu, E.; Chu, T.Y.; Ray, P.; Traktman, P.; Besmer, P. Molecular bases of dominant negative and loss of function mutations at the murine c-kit/white spotting locus: W37, Wv, W41 and W. EMBO J 1990, 9, 1805–1813.
[87]
Reith, A.D.; Rottapel, R.; Giddens, E.; Brady, C.; Forrester, L.; Bernstein, A. W mutant mice with mild or severe developmental defects contain distinct point mutations in the kinase domain of the c-kit receptor. Gene. Dev 1990, 4, 390–400.
[88]
Grimbaldeston, M.A.; Chen, C.C.; Piliponsky, A.M.; Tsai, M.; Tam, S.Y.; Galli, S.J. Mast cell-deficient W-sash c-kit mutant Kit W-sh/W-sh mice as a model for investigating mast cell biology in vivo. Am. J. Pathol 2005, 167, 835–848.
[89]
Robbie-Ryan, M.; Tanzola, M.B.; Secor, V.H.; Brown, M.A. Cutting edge: Both activating and inhibitory Fc receptors expressed on mast cells regulate experimental allergic encephalomyelitis disease severity. J. Immunol 2003, 170, 1630–1634.
[90]
Sayed, B.A.; Christy, A.L.; Walker, M.E.; Brown, M.A. Meningeal mast cells affect early T cell central nervous system infiltration and blood-brain barrier integrity through TNF: A role for neutrophil recruitment? J. Immunol 2010, 184, 6891–6900.
[91]
Sayed, B.A.; Walker, M.E.; Brown, M.A. Cutting edge: Mast cells regulate disease severity in a relapsing-remitting model of multiple sclerosis. J. Immunol 2011, 186, 3294–3298.
[92]
Bennett, J.L.; Blanchet, M.R.; Zhao, L.; Zbytnuik, L.; Antignano, F.; Gold, M.; Kubes, P.; McNagny, K.M. Bone marrow-derived mast cells accumulate in the central nervous system during inflammation but are dispensable for experimental autoimmune encephalomyelitis pathogenesis. J. Immunol 2009, 182, 5507–5514.
[93]
Norman, M.U.; Hwang, J.; Hulliger, S.; Bonder, C.S.; Yamanouchi, J.; Santamaria, P.; Kubes, P. Mast cells regulate the magnitude and the cytokine microenvironment of the contact hypersensitivity response. Am. J. Pathol 2008, 172, 1638–1649.
[94]
Piliponsky, A.M.; Chen, C.C.; Grimbaldeston, M.A.; Burns-Guydish, S.M.; Hardy, J.; Kalesnikoff, J.; Contag, C.H.; Tsai, M.; Galli, S.J. Mast cell-derived TNF can exacerbate mortality during severe bacterial infections in C57BL/6-KitW-sh/W-sh mice. Am. J. Pathol 2010, 176, 926–938.
[95]
Williams, C.M.; Galli, S.J. Mast cells can amplify airway reactivity and features of chronic inflammation in an asthma model in mice. J. Exp. Med 2000, 192, 455–462.
[96]
Lyon, M.F.; Glenister, P.H. A new allele sash (Wsh) at the W-locus and a spontaneous recessive lethal in mice. Genet. Res 1982, 39, 315–322.
[97]
Nigrovic, P.A.; Gray, D.H.; Jones, T.; Hallgren, J.; Kuo, F.C.; Chaletzky, B.; Gurish, M.; Mathis, D.; Benoist, C.; Lee, D.M. Genetic inversion in mast cell-deficient (Wsh) mice interrupts corin and manifests as hematopoietic and cardiac aberrancy. Am. J. Pathol 2008, 173, 1693–1701.
Li, H.; Nourbakhsh, B.; Safavi, F.; Li, K.; Xu, H.; Cullimore, M.; Zhou, F.; Zhang, G.; Rostami, A. Kit (W-sh) mice develop earlier and more severe experimental autoimmune encephalomyelitis due to absence of immune suppression. J. Immunol 2011, 187, 274–282.
Musio, S.; Gallo, B.; Scabeni, S.; Lapilla, M.; Poliani, P.L.; Matarese, G.; Ohtsu, H.; Galli, S.J.; Mantegazza, R.; Steinman, L.; et al. A key regulatory role for histamine in experimental autoimmune encephalomyelitis: Disease exacerbation in histidine decarboxylase-deficient mice. J. Immunol 2006, 176, 17–26.
[102]
Nautiyal, K.M.; Ribeiro, A.C.; Pfaff, D.W.; Silver, R. Brain mast cells link the immune system to anxiety-like behavior. Proc. Natl. Acad. Sci. USA 2008, 105, 18053–18057.
[103]
Lu, C.; Diehl, S.A.; Noubade, R.; Ledoux, J.; Nelson, M.T.; Spach, K.; Zachary, J.F.; Blankenhorn, E.P.; Teuscher, C. Endothelial histamine H1 receptor signaling reduces blood-brain barrier permeability and susceptibility to autoimmune encephalomyelitis. Proc. Natl. Acad. Sci. USA 2010, 107, 18967–18972.
[104]
Teuscher, C.; Subramanian, M.; Noubade, R.; Gao, J.F.; Offner, H.; Zachary, J.F.; Blankenhorn, E.P. Central histamine H3 receptor signaling negatively regulates susceptibility to autoimmune inflammatory disease of the CNS. Proc. Natl. Acad. Sci. USA 2007, 104, 10146–10151.
[105]
Lapilla, M.; Gallo, B.; Martinello, M.; Procaccini, C.; Costanza, M.; Musio, S.; Rossi, B.; Angiari, S.; Farina, C.; Steinman, L.; et al. Histamine regulates autoreactive T cell activation and adhesiveness in inflamed brain microcirculation. J. Leukoc. Biol 2011, 89, 259–267.
[106]
Charles, N.; Hardwick, D.; Daugas, E.; Illei, G.G.; Rivera, J. Basophils and the T helper 2 environment can promote the development of lupus nephritis. Nat. Med 2010, 16, 701–707.
