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Gene Review

Hand1  -  heart and neural crest derivatives...

Mus musculus

Synonyms: Ehand, Ehand1, Extraembryonic tissues, heart, autonomic nervous system and neural crest derivatives-expressed protein 1, Heart-and neural crest derivatives-expressed protein 1, Helix-loop-helix transcription factor expressed in extraembryonic mesoderm and trophoblast, ...
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Disease relevance of Hand1


Psychiatry related information on Hand1

  • Alcohol consumption alters antigen-specific Th1 responses: mechanisms of deficit and repair [6].
  • We have investigated the anti-tumour activity of CD4+ BALB/c Th1 and Th2 clones which recognize a processed Id of the syngeneic lambda 2(315) L chain in the context of the class II MHC molecule I-Ed [7].

High impact information on Hand1

  • Interleukin-18 regulates both Th1 and Th2 responses [8].
  • In principle, IL-18 enhances the IL-12-driven Th1 immune responses, but it can also stimulate Th2 immune responses in the absence of IL-12 [8].
  • Interleukin-12 (IL-12) is a heterodimeric cytokine that plays a central role in promoting type 1 T helper cell (Th1) responses and, hence, cell-mediated immunity [9].
  • Inhibition of IL-12 synthesis or activity may be beneficial in diseases associated with pathologic Th1 responses, such as multiple sclerosis or Crohn's disease [9].
  • IL-12 and IL-12-induced IFN-gamma favor Th1 cell differentiation by priming CD4+ T cells for high IFN-gamma production; and 3 [10].

Chemical compound and disease context of Hand1


Biological context of Hand1


Anatomical context of Hand1


Associations of Hand1 with chemical compounds

  • In the present study, we have shown that some EDC [benzophenone, p-octylphenol, and tributyltin chloride (TBT)] promoted strong Th2 polarization via suppression and augmentation of Th1 and Th2 development, respectively, from naive CD4(+) T cells primed with anti-CD3 and splenic antigen-presenting cells (APC) [21].
  • Additionally, an increase in Th2-type and a decrease in Th1-type cytokines could be detected in vitro after incubation with dydrogesterone [22].
  • The present results indicated that hyposensitization with the GMFA can desensitize or down-regulate the allergic response in Balb/c mice and this hypoallergenic variant of ovomucoid DIII can shift an ongoing allergen-specific Th2 response towards a Th1 skewed response [11].
  • Consistent with their maturational status, these nicDCs have reduced capacity for antigen uptake and produce substantially less Th1-promoting cytokine, IL-12, in response to Th1-polarizing adjuvant, lipopolysaccharide (LPS) [23].
  • In the absence of local histamine the cytokine balance is shifted toward Th1 types at the maternal-placental interface, threatening pregnancy [24].

Physical interactions of Hand1

  • In this study we have compared the regulatory effects of both IL-4 and IL-10 on the development of a more complex Th1 effector function in vivo, the development of delayed-type hypersensitivity (DTH) to Leishmania major in mice immune to Leishmania [25].
  • Binding experiments in cotransfected 293 T cells and in vitro revealed that Sox15 interacted with Hand1 [26].
  • Nevertheless, in defined experimental systems, the interaction between T-cell receptor (TCR), peptide and major histocompatibility complex (MHC) can determine Th1/Th2 dominance [27].
  • In addition, other protein complexes with NF-kappa B binding sequences were seen using lysates from Th1 and Th0 cells but not Th2 cells [28].
  • Using a system in which priming leads to responses dominated by one or the other of these cell types, we show that varying either the antigenic peptide or the major histocompatibility complex class II molecule can determine whether Th1-like or Th2-like responses are obtained [29].

Regulatory relationships of Hand1

  • The pump was inducible in Th1 cells by antigenic stimulation in vitro leading to equal expression in activated Th1 and Th2 cell clones [30].
  • The results also suggest that Th1 responses may be more preferentially suppressed by the SINOMENIUM ACUTUM-derived alkaloid compared to Th2 responses [31].
  • In contrast IL-10 remained unchanged again suggesting that AGB critically influenced Th1 profile of the cytokines [32].
  • Conclusions: These results indicated that oral administration of CpG ODN-OVA conjugate significantly induced antigen-specific Th1 responses and reduced Th2 responses (allergic reactions) on re-stimulation [33].
  • Surface P-selectin glycoprotein ligand 1 (PSGL-1) and LFA-1 were up-regulated on both populations but were expressed at higher levels on Th1-like cells [34].

Other interactions of Hand1

  • dHAND and eHAND are related basic helix-loop-helix (bHLH) transcription factors that are expressed in mesodermal and neural crest-derived structures of the developing heart [35].
  • Moreover, the expression of suppressor of cytokine signaling (SOCS)-1, SOCS-3, and repressor of GATA-3 (ROG) favored a predominant Th1 cytokine response in CDD-fed mice [36].
  • In this study, we describe that ERK1(-/-) mice display a bias toward Th1 type immune response [3].
  • CCR2 is required for monocyte recruitment in many inflammatory processes, as well as conferring Th1 lymphokine responses [37].
  • The transduced MBP-specific Th1 cells were found to lose the capacity to provoke EAE in BALB/c mice, and to gain instead the ability to protect against EAE in (SJLxBALB/c) F1 mice immunized with proteolipid protein (PLP) [38].

Analytical, diagnostic and therapeutic context of Hand1

  • Fluorescence-activated cell-sorting revealed that the lymphokine response (Th1 or Th2, respectively) to L. major antigens was restricted to this dye-extruding subset [30].
  • RNA in situ hybridization and reverse transcriptase-PCR demonstrate a stage- and tissue-specific distribution for the expression of Th1 [39].
  • It is concluded that this way of vaccination induced a concurrent Th1/ Th2 local and systemic responses that are protective and at the same time they may help balancing the strong Th2 response triggered by helminth infections [40].
  • To determine Th1/Th2 cytokine production by lymphocytes, lymphocytes of DS-Nh mice fed TBT and of controls were cultured with staphylococcal enterotoxin B and cytokine levels in the supernatants were measured by ELISA [41].
  • T lymphocytes obtained from DNA-vaccinated mice showed clearly distinguished comparative RT-PCR analysis of cytokine mRNA expression for Th1 and Th2 immune responses compared to T lymphocytes obtained from control animals injected with vector DNA [42].


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  2. Effects of interleukin 12 on immune responses and host protection in mice infected with intestinal nematode parasites. Finkelman, F.D., Madden, K.B., Cheever, A.W., Katona, I.M., Morris, S.C., Gately, M.K., Hubbard, B.R., Gause, W.C., Urban, J.F. J. Exp. Med. (1994) [Pubmed]
  3. ERK1-/- Mice Exhibit Th1 Cell Polarization and Increased Susceptibility to Experimental Autoimmune Encephalomyelitis. Agrawal, A., Dillon, S., Denning, T.L., Pulendran, B. J. Immunol. (2006) [Pubmed]
  4. Th1 and Type 1 Cytotoxic T Cells Dominate Responses in T-bet Overexpression Transgenic Mice That Develop Contact Dermatitis. Ishizaki, K., Yamada, A., Yoh, K., Nakano, T., Shimohata, H., Maeda, A., Fujioka, Y., Morito, N., Kawachi, Y., Shibuya, K., Otsuka, F., Shibuya, A., Takahashi, S. J. Immunol. (2007) [Pubmed]
  5. Spontaneous Large-Scale Lymphoid Neogenesis and Balanced Autoimmunity versus Tolerance in the Stomach of H+/K+-ATPase-Reactive TCR Transgenic Mouse. Katakai, T., Nomura, T., Gonda, H., Sugai, M., Agata, Y., Nishio, A., Masuda, T., Sakaguchi, S., Shimizu, A. J. Immunol. (2006) [Pubmed]
  6. Alcohol consumption alters antigen-specific Th1 responses: mechanisms of deficit and repair. Waltenbaugh, C., Vasquez, K., Peterson, J.D. Alcohol. Clin. Exp. Res. (1998) [Pubmed]
  7. Anti-tumour activity of idiotype-specific, MHC-restricted Th1 and Th2 clones in vitro and in vivo. Lauritzsen, G.F., Weiss, S., Bogen, B. Scand. J. Immunol. (1993) [Pubmed]
  8. Interleukin-18 regulates both Th1 and Th2 responses. Nakanishi, K., Yoshimoto, T., Tsutsui, H., Okamura, H. Annu. Rev. Immunol. (2001) [Pubmed]
  9. The interleukin-12/interleukin-12-receptor system: role in normal and pathologic immune responses. Gately, M.K., Renzetti, L.M., Magram, J., Stern, A.S., Adorini, L., Gubler, U., Presky, D.H. Annu. Rev. Immunol. (1998) [Pubmed]
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  11. Engineered recombinant ovomucoid third domain can desensitize Balb/c mice of egg allergy. Rupa, P., Mine, Y. Allergy (2006) [Pubmed]
  12. Dietary arginine enhances adhesion molecule and T helper 2 cytokine expression in mice with gut-derived sepsis. Yeh, C.L., Hsu, C.S., Chiu, W.C., Hou, Y.C., Yeh, S.L. Shock (2006) [Pubmed]
  13. Comparison of phage pVIII and KLH as vector in inducing the production of cytokines in C57BL/6J mice. Su, Q.P., Wen, D.Z., Yang, Q., Zhang, Y.H., Liu, C., Wang, L. Vaccine (2007) [Pubmed]
  14. The biology of chemokines and their receptors. Rossi, D., Zlotnik, A. Annu. Rev. Immunol. (2000) [Pubmed]
  15. The HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease. Youssef, S., Stüve, O., Patarroyo, J.C., Ruiz, P.J., Radosevich, J.L., Hur, E.M., Bravo, M., Mitchell, D.J., Sobel, R.A., Steinman, L., Zamvil, S.S. Nature (2002) [Pubmed]
  16. The Hand1 bHLH transcription factor is essential for placentation and cardiac morphogenesis. Riley, P., Anson-Cartwright, L., Cross, J.C. Nat. Genet. (1998) [Pubmed]
  17. Heart and extra-embryonic mesodermal defects in mouse embryos lacking the bHLH transcription factor Hand1. Firulli, A.B., McFadden, D.G., Lin, Q., Srivastava, D., Olson, E.N. Nat. Genet. (1998) [Pubmed]
  18. Differential regulation of Hand1 homodimer and Hand1-E12 heterodimer activity by the cofactor FHL2. Hill, A.A., Riley, P.R. Mol. Cell. Biol. (2004) [Pubmed]
  19. Requirement of the mouse I-mfa gene for placental development and skeletal patterning. Kraut, N., Snider, L., Chen, C.M., Tapscott, S.J., Groudine, M. EMBO J. (1998) [Pubmed]
  20. Role of Hand1/eHAND in the dorso-ventral patterning and interventricular septum formation in the embryonic heart. Togi, K., Kawamoto, T., Yamauchi, R., Yoshida, Y., Kita, T., Tanaka, M. Mol. Cell. Biol. (2004) [Pubmed]
  21. Endocrine disruptors that deplete glutathione levels in APC promote Th2 polarization in mice leading to the exacerbation of airway inflammation. Kato, T., Tada-Oikawa, S., Takahashi, K., Saito, K., Wang, L., Nishio, A., Hakamada-Taguchi, R., Kawanishi, S., Kuribayashi, K. Eur. J. Immunol. (2006) [Pubmed]
  22. The progesterone derivative dydrogesterone down-regulates neurokinin 1 receptor expression on lymphocytes, induces a Th2 skew and exerts hypoalgesic effects in mice. Orsal, A.S., Blois, S., Labuz, D., Peters, E.M., Schaefer, M., Arck, P.C. J. Mol. Med. (2006) [Pubmed]
  23. Nicotine alters the biological activities of developing mouse bone marrow-derived dendritic cells (DCs). Nouri-Shirazi, M., Tinajero, R., Guinet, E. Immunol. Lett. (2007) [Pubmed]
  24. Histamine Regulates Placental Cytokine Expression - In vivo Study on HDC Knockout Mice. Pap, E., Falus, A., Mih??lyi, D., Borck, H., Diel, F., P??llinger, E. Placenta (2007) [Pubmed]
  25. Interleukin-4 and interleukin-10 synergize to inhibit cell-mediated immunity in vivo. Powrie, F., Menon, S., Coffman, R.L. Eur. J. Immunol. (1993) [Pubmed]
  26. Sox15 enhances trophoblast giant cell differentiation induced by Hand1 in mouse placenta. Yamada, K., Kanda, H., Tanaka, S., Takamatsu, N., Shiba, T., Ito, M. Differentiation (2006) [Pubmed]
  27. How the MHC selects Th1/Th2 immunity. Murray, J.S. Immunol. Today (1998) [Pubmed]
  28. Regulation of cytokine gene expression in T helper cell subsets. Lederer, J.A., Liou, J.S., Todd, M.D., Glimcher, L.H., Lichtman, A.H. J. Immunol. (1994) [Pubmed]
  29. Altered peptide ligands can control CD4 T lymphocyte differentiation in vivo. Pfeiffer, C., Stein, J., Southwood, S., Ketelaar, H., Sette, A., Bottomly, K. J. Exp. Med. (1995) [Pubmed]
  30. A multidrug-resistance protein (MRP)-like transmembrane pump is highly expressed by resting murine T helper (Th) 2, but not Th1 cells, and is induced to equal expression levels in Th1 and Th2 cells after antigenic stimulation in vivo. Lohoff, M., Prechtl, S., Sommer, F., Roellinghoff, M., Schmitt, E., Gradehandt, G., Rohwer, P., Stride, B.D., Cole, S.P., Deeley, R.G. J. Clin. Invest. (1998) [Pubmed]
  31. Suppression of Th1 and Th2 Immune Responses in Mice by Sinomenine, an Alkaloid Extracted from the Chinese Medicinal Plant Sinomenium acutum. Feng, H., Yamaki, K., Takano, H., Inoue, K., Yanagisawa, R., Yoshino, S. Planta Med. (2006) [Pubmed]
  32. A standardized root extract of Withania somnifera and its major constituent withanolide-A elicit humoral and cell-mediated immune responses by up regulation of Th1-dominant polarization in BALB/c mice. Malik, F., Singh, J., Khajuria, A., Suri, K.A., Satti, N.K., Singh, S., Kaul, M.K., Kumar, A., Bhatia, A., Qazi, G.N. Life Sci. (2007) [Pubmed]
  33. Effect of Oral Administration of CpG ODN-OVA on WBB6F1-W/Wv Mice. Teshima, R., Okunuki, H., Sato, Y., Akiyama, H., Maitani, T., Sawada, J. Allergology international : official journal of the Japanese Society of Allergology. (2006) [Pubmed]
  34. Recruitment of IFN-gamma-producing (Th1-like) cells into the inflamed retina in vivo is preferentially regulated by P-selectin glycoprotein ligand 1:P/E-selectin interactions. Xu, H., Manivannan, A., Jiang, H.R., Liversidge, J., Sharp, P.F., Forrester, J.V., Crane, I.J. J. Immunol. (2004) [Pubmed]
  35. Regulation of cardiac mesodermal and neural crest development by the bHLH transcription factor, dHAND. Srivastava, D., Thomas, T., Lin, Q., Kirby, M.L., Brown, D., Olson, E.N. Nat. Genet. (1997) [Pubmed]
  36. Favored T helper 1 response in a mouse model of hepatosteatosis is associated with enhanced T cell-mediated hepatitis. Kremer, M., Hines, I.N., Milton, R.J., Wheeler, M.D. Hepatology (2006) [Pubmed]
  37. Targeted deletion of CCR2 impairs deep vein thombosis resolution in a mouse model. Henke, P.K., Pearce, C.G., Moaveni, D.M., Moore, A.J., Lynch, E.M., Longo, C., Varma, M., Dewyer, N.A., Deatrick, K.B., Upchurch, G.R., Wakefield, T.W., Hogaboam, C., Kunkel, S.L. J. Immunol. (2006) [Pubmed]
  38. When engineered to produce latent TGF-beta1, antigen specific T cells down regulate Th1 cell-mediated autoimmune and Th2 cell-mediated allergic inflammatory processes. Thorbecke, G.J., Umetsu, D.T., deKruyff, R.H., Hansen, G., Chen, L.Z., Hochwald, G.M. Cytokine Growth Factor Rev. (2000) [Pubmed]
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  40. Vaccination of mice against intestinal Trichinella spiralis infections by oral administration of antigens microencapsulated in methacrilic acid copolymers. Dea-Ayuela, M.A., Rama-Iñiguez, S., Bolas-Fernández, F. Vaccine (2006) [Pubmed]
  41. Effects of Tributyltin on the Development of Atopic Dermatitis-Like Eruptions in DS-Nh Mice. Iwamura, C., Aihara, M., Nakazawa, M., Takahashi, K., Yoshioka, N., Matsukura, S., Hirasawa, T., Minami, M., Ikezawa, Z. Int. Arch. Allergy Immunol. (2006) [Pubmed]
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