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Gene Review

NELFCD  -  negative elongation factor complex member C/D

Homo sapiens

Synonyms: HSPC130, NELF-C, NELF-C/D, NELF-D, NELFD, ...
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Disease relevance of TH1L


Psychiatry related information on TH1L

  • They act as a negative regulator of activated T cells, control immunoglobulin production, contribute to the regulation of the TH1/TH2 balance, and occupy a central role in anti-viral defense mechanisms [6].
  • Drug abuse may alter the change from the (CD4+)CD45RA+ to the (CD4+)CD45RA- phenotype selectively, which recovers in HIV-1+ methamphetamine abusers during treatment from baseline to 4-weeks, as manifested by improved IL-2 production in vitro. of TH1 and TH2 cytokines during progression to AIDS [7].

High impact information on TH1L


Chemical compound and disease context of TH1L

  • We report the construction of a single adenovirus encoding human tyrosine hydroxylase 1 (hTH-1) under the negative control of the tetracycline-based gene regulatory system [13].
  • The clinical effects of glatiramer acetate (GA), an approved therapy for multiple sclerosis, are thought to be largely mediated by a T-helper 1 (TH1) to T-helper 2 (TH2) shift of GA-reactive T-lymphocytes [14].
  • TH1/TH2 cytokines and inflammatory cells in skin biopsy specimens from patients with chronic idiopathic urticaria: comparison with the allergen-induced late-phase cutaneous reaction [15].
  • Before dehydration, > 90% of the iron in hTH1 had Mössbauer parameters typical for high-spin Fe(II) in a six-coordinate environment [isomer shift delta (1.8-77 K) = 1.26-1.24 mm s-1 and quadrupole splitting delta EQ = 2.68 mm s-1] [16].
  • Full-length human tyrosine hydroxylase 1 (hTH1) and a truncated enzyme lacking the 150 N-terminal amino acids were expressed in Escherichia coli and purified either with or without (6 x histidine) N-terminal tags [16].

Biological context of TH1L

  • Furthermore, we observed that TH1 inhibited cell cycle progression in TH1 stably transfected 7721 cells compared with mock cells, and flow cell cytometry analysis suggested that the TH1 stably transfected 7721 cells were G(0)/G(1) phase-arrested [17].
  • In a two-hybrid screen of human fetal liver cDNA library, TH1 was detected as a new interaction partner of A-Raf [18].
  • These results indicate that a switch from the TH1 to the TH2 cytokine phenotype does not occur during the progression of HIV disease [19].
  • Interleukin-12 (IL-12) is a cytokine that promotes cell-mediated immunity to intracellular pathogens by inducing type 1 helper T cell (TH1) responses and interferon-gamma (IFN-gamma) production [20].
  • Thus, Rac2 activates TH1-specific signaling and IFN-gamma gene expression [12].

Anatomical context of TH1L

  • It is not known whether subsets of dendritic cells provide different cytokine microenvironments that determine the differentiation of either type-1 T helper (TH1) or TH2 cells [21].
  • Thus, a negative feedback loop from the mature T helper cells may selectively inhibit prolonged TH1 or TH2 responses by regulating survival of the appropriate dendritic cell subset [21].
  • TH1 and TH2 cytokine control of thyrocyte survival in thyroid autoimmunity [22].
  • CONCLUSION--Whereas TH1-type immunity to trophoblast is associated with URA and may play a role in reproductive failure, TH2-type immunity may be a natural response to trophoblast contributing to successful pregnancy [23].
  • Regulation of TH1- and TH2-type cytokine expression and action in atopic asthmatic sensitized airway smooth muscle [24].

Associations of TH1L with chemical compounds

  • HBEC thus drive the effector end of a TH1-controlled feedback loop, which protects airway mucosal tissues at the potential lesional site in asthma from overwhelming CD4+ TH2 (and potentially TH1) responses following allergen exposure [25].
  • In the presence of PGE2, TH1-like responses are suppressed and TH0-like responses are shifted toward a TH2-like pattern dominated by the production of IL-4 and IL-5 [26].
  • The effect of serine 19 phosphorylation on serine 40 (44 in TH2) phosphorylation is stronger in TH2 than in TH1 [27].
  • TH0, TH1, and TH2 T cell clones were stimulated in the presence and absence of the prostaglandin E1 (PGE1) analog misoprostol and PGE2 [26].
  • Recently, it was reported that histamine induced IL-18 and that IL-18 might act as a coinducer of TH1 and TH2 cytokines [28].

Other interactions of TH1L

  • The binding between A-Raf and TH1 was specific, as no binding between TH1 and B-Raf or c-Raf was observed, and the amino-terminal 162 amino acids in the A-Raf regulatory domain were found to be sufficient for this interaction [18].
  • Sustained T-bet expression confers polarized human TH2 cells with TH1-like cytokine production and migratory capacities [29].
  • The results show that both IFN-gamma producing (Th1-like) and IL-4 producing (Th2-like) T cells recognizing LPGAP are expanded after infection with L. donovani in humans [30].
  • In addition, in activated T helper lymphocyte clones, it has been demonstrated that IFN-gamma (TH1-like cytokine) and IL-5 (TH2-like cytokine) are differentially regulated by the AC system [31].
  • Induction of systemic TH1-like innate immunity in normal volunteers following subcutaneous but not intravenous administration of CPG 7909, a synthetic B-class CpG oligodeoxynucleotide TLR9 agonist [32].

Analytical, diagnostic and therapeutic context of TH1L

  • Using confocal microscopy, we found that TH1 colocalizes with A-Raf, which confirms our former results [17].
  • CONCLUSIONS: Immunotherapy with AS101 enhances TH1 function while interfering with the TH2 response [33].
  • Our results indicate that intranodal vaccination with semimature DCs can prime strong, long-lasting CD4 T-cell responses with a TH1-type cytokine profile in cancer patients [34].
  • These results suggest that G-CSF decreases IFN-gamma and increases IL-4 production in vitro and in vivo and likely modulates a balance between TH1 and TH2 cells, an effect that may be important in PBSC transplantation [35].
  • The TH1/TH2 imbalance was more related to TH2 over-expression than to TH1 deficiency and persisted for at least 1 year under HAART [36].


  1. Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma. Robinson, D.S., Hamid, Q., Ying, S., Tsicopoulos, A., Barkans, J., Bentley, A.M., Corrigan, C., Durham, S.R., Kay, A.B. N. Engl. J. Med. (1992) [Pubmed]
  2. A synthetic glycolipid prevents autoimmune encephalomyelitis by inducing TH2 bias of natural killer T cells. Miyamoto, K., Miyake, S., Yamamura, T. Nature (2001) [Pubmed]
  3. Ability of HIV to promote a TH1 to TH0 shift and to replicate preferentially in TH2 and TH0 cells. Maggi, E., Mazzetti, M., Ravina, A., Annunziato, F., de Carli, M., Piccinni, M.P., Manetti, R., Carbonari, M., Pesce, A.M., del Prete, G. Science (1994) [Pubmed]
  4. Selective expression of the eotaxin receptor CCR3 by human T helper 2 cells. Sallusto, F., Mackay, C.R., Lanzavecchia, A. Science (1997) [Pubmed]
  5. Plasmacytoid dendritic cells activated by influenza virus and CD40L drive a potent TH1 polarization. Cella, M., Facchetti, F., Lanzavecchia, A., Colonna, M. Nat. Immunol. (2000) [Pubmed]
  6. The defect of the perforin granule system in cytotoxic T lymphocytes of atopic patients--are perforin reduction and hyperreleasability of clinical relevance? Ambach, A., Bonnekoh, B., Gollnick, H. Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG. (2003) [Pubmed]
  7. Cellular immunology in HIV-1 positive African American women using alcohol and cocaine. Chiappelli, F., Shapshak, P., Younai, F., McCoy, C., Page, B., Prolo, P. Front. Biosci. (2006) [Pubmed]
  8. TWEAK attenuates the transition from innate to adaptive immunity. Maecker, H., Varfolomeev, E., Kischkel, F., Lawrence, D., LeBlanc, H., Lee, W., Hurst, S., Danilenko, D., Li, J., Filvaroff, E., Yang, B., Daniel, D., Ashkenazi, A. Cell (2005) [Pubmed]
  9. Involvement of receptor-interacting protein 2 in innate and adaptive immune responses. Chin, A.I., Dempsey, P.W., Bruhn, K., Miller, J.F., Xu, Y., Cheng, G. Nature (2002) [Pubmed]
  10. Histamine regulates T-cell and antibody responses by differential expression of H1 and H2 receptors. Jutel, M., Watanabe, T., Klunker, S., Akdis, M., Thomet, O.A., Malolepszy, J., Zak-Nejmark, T., Koga, R., Kobayashi, T., Blaser, K., Akdis, C.A. Nature (2001) [Pubmed]
  11. Insulin-dependent diabetes mellitus as an autoimmune disease. Bach, J.F. Endocr. Rev. (1994) [Pubmed]
  12. Role of the guanosine triphosphatase Rac2 in T helper 1 cell differentiation. Li, B., Yu, H., Zheng, W., Voll, R., Na, S., Roberts, A.W., Williams, D.A., Davis, R.J., Ghosh, S., Flavell, R.A. Science (2000) [Pubmed]
  13. A single adenovirus vector mediates doxycycline-controlled expression of tyrosine hydroxylase in brain grafts of human neural progenitors. Corti, O., Sabaté, O., Horellou, P., Colin, P., Dumas, S., Buchet, D., Buc-Caron, M.H., Mallet, J. Nat. Biotechnol. (1999) [Pubmed]
  14. Glatiramer acetate-specific T-helper 1- and 2-type cell lines produce BDNF: implications for multiple sclerosis therapy. Brain-derived neurotrophic factor. Ziemssen, T., Kümpfel, T., Klinkert, W.E., Neuhaus, O., Hohlfeld, R. Brain (2002) [Pubmed]
  15. TH1/TH2 cytokines and inflammatory cells in skin biopsy specimens from patients with chronic idiopathic urticaria: comparison with the allergen-induced late-phase cutaneous reaction. Ying, S., Kikuchi, Y., Meng, Q., Kay, A.B., Kaplan, A.P. J. Allergy Clin. Immunol. (2002) [Pubmed]
  16. Iron coordination geometry in full-length, truncated, and dehydrated forms of human tyrosine hydroxylase studied by Mössbauer and X-ray absorption spectroscopy. Schünemann, V., Meier, C., Meyer-Klaucke, W., Winkler, H., Trautwein, A.X., Knappskog, P.M., Toska, K., Haavik, J. J. Biol. Inorg. Chem. (1999) [Pubmed]
  17. Trihydrophobin 1 is a new negative regulator of A-Raf kinase. Liu, W., Shen, X., Yang, Y., Yin, X., Xie, J., Yan, J., Jiang, J., Liu, W., Wang, H., Sun, M., Zheng, Y., Gu, J. J. Biol. Chem. (2004) [Pubmed]
  18. Identification of TH1 as an interaction partner of A-Raf kinase. Yin, X.L., Chen, S., Gu, J.X. Mol. Cell. Biochem. (2002) [Pubmed]
  19. Lack of evidence for the dichotomy of TH1 and TH2 predominance in HIV-infected individuals. Graziosi, C., Pantaleo, G., Gantt, K.R., Fortin, J.P., Demarest, J.F., Cohen, O.J., Sékaly, R.P., Fauci, A.S. Science (1994) [Pubmed]
  20. Severe mycobacterial and Salmonella infections in interleukin-12 receptor-deficient patients. de Jong, R., Altare, F., Haagen, I.A., Elferink, D.G., Boer, T., van Breda Vriesman, P.J., Kabel, P.J., Draaisma, J.M., van Dissel, J.T., Kroon, F.P., Casanova, J.L., Ottenhoff, T.H. Science (1998) [Pubmed]
  21. Reciprocal control of T helper cell and dendritic cell differentiation. Rissoan, M.C., Soumelis, V., Kadowaki, N., Grouard, G., Briere, F., de Waal Malefyt, R., Liu, Y.J. Science (1999) [Pubmed]
  22. TH1 and TH2 cytokine control of thyrocyte survival in thyroid autoimmunity. Mirakian, R., Hammond, L.J., Bottazzo, G.F. Nat. Immunol. (2001) [Pubmed]
  23. T-helper 1-type immunity to trophoblast in women with recurrent spontaneous abortion. Hill, J.A., Polgar, K., Anderson, D.J. JAMA (1995) [Pubmed]
  24. Regulation of TH1- and TH2-type cytokine expression and action in atopic asthmatic sensitized airway smooth muscle. Hakonarson, H., Maskeri, N., Carter, C., Grunstein, M.M. J. Clin. Invest. (1999) [Pubmed]
  25. Human bronchial epithelium controls TH2 responses by TH1-induced, nitric oxide-mediated STAT5 dephosphorylation: implications for the pathogenesis of asthma. Eriksson, U., Egermann, U., Bihl, M.P., Gambazzi, F., Tamm, M., Holt, P.G., Bingisser, R.M. J. Immunol. (2005) [Pubmed]
  26. Modulation of helper T cell function by prostaglandins. Gold, K.N., Weyand, C.M., Goronzy, J.J. Arthritis Rheum. (1994) [Pubmed]
  27. Differential regulation of the human tyrosine hydroxylase isoforms via hierarchical phosphorylation. Lehmann, I.T., Bobrovskaya, L., Gordon, S.L., Dunkley, P.R., Dickson, P.W. J. Biol. Chem. (2006) [Pubmed]
  28. IL-18 might reflect disease activity in mild and moderate asthma exacerbation. Tanaka, H., Miyazaki, N., Oashi, K., Teramoto, S., Shiratori, M., Hashimoto, M., Ohmichi, M., Abe, S. J. Allergy Clin. Immunol. (2001) [Pubmed]
  29. Sustained T-bet expression confers polarized human TH2 cells with TH1-like cytokine production and migratory capacities. Lametschwandtner, G., Biedermann, T., Schwärzler, C., Günther, C., Kund, J., Fassl, S., Hinteregger, S., Carballido-Perrig, N., Szabo, S.J., Glimcher, L.H., Carballido, J.M. J. Allergy Clin. Immunol. (2004) [Pubmed]
  30. Production of interferon-gamma and interleukin-4 by human T cells recognizing Leishmania lipophosphoglycan-associated protein. Kemp, M., Kurtzhals, J.A., Christensen, C.B., Kharazmi, A., Jardim, A., Bendtzen, K., Gachihi, G.S., Olafson, R.W., Theander, T.G. Immunol. Lett. (1993) [Pubmed]
  31. Allergen challenge primes for IL-5 mRNA production and abrogates beta-adrenergic function in peripheral blood T lymphocytes from asthmatics. Borger, P., Jonker, G.J., Vellenga, E., Postma, D.S., De Monchy, J.G., Kauffman, H.F. Clin. Exp. Allergy (1999) [Pubmed]
  32. Induction of systemic TH1-like innate immunity in normal volunteers following subcutaneous but not intravenous administration of CPG 7909, a synthetic B-class CpG oligodeoxynucleotide TLR9 agonist. Krieg, A.M., Efler, S.M., Wittpoth, M., Al Adhami, M.J., Davis, H.L. J. Immunother. (2004) [Pubmed]
  33. Predominance of TH1 response in tumor-bearing mice and cancer patients treated with AS101. Sredni, B., Tichler, T., Shani, A., Catane, R., Kaufman, B., Strassmann, G., Albeck, M., Kalechman, Y. J. Natl. Cancer Inst. (1996) [Pubmed]
  34. Intranodal injection of semimature monocyte-derived dendritic cells induces T helper type 1 responses to protein neoantigen. Gilliet, M., Kleinhans, M., Lantelme, E., Schadendorf, D., Burg, G., Nestle, F.O. Blood (2003) [Pubmed]
  35. Pharmacologic doses of granulocyte colony-stimulating factor affect cytokine production by lymphocytes in vitro and in vivo. Sloand, E.M., Kim, S., Maciejewski, J.P., Van Rhee, F., Chaudhuri, A., Barrett, J., Young, N.S. Blood (2000) [Pubmed]
  36. Persistent alterations in T-cell repertoire, cytokine and chemokine receptor gene expression after 1 year of highly active antiretroviral therapy. Martinon, F., Michelet, C., Peguillet, I., Taoufik, Y., Lefebvre, P., Goujard, C., Guillet, J.G., Delfraissy, J.F., Lantz, O. AIDS (1999) [Pubmed]
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