Neuroimmune Semaphorins As Costimulatory Molecules and Beyond

Overview

Journal Mol Med

Publisher Biomed Central

Specialties General Medicine
Molecular Biology

Date 2018 Aug 24

PMID 30134791

Citations 8

Authors

Svetlana P Chapoval

Affiliations

Soon will be listed here.

Abstract

Several neuronal guidance proteins, known as semaphorin molecules, function in the immune system. This dual tissue performance has led to them being defined as "neuroimmune semaphorins". They have been shown to regulate T cell activation by serving as costimulatory molecules. Similar to classical costimulatory molecules, neuroimmune semaphorins are either constitutively or inducibly expressed on immune cells. In contrast to the classical costimulatory molecule function, the action of neuroimmune semaphorins requires the presence of two signals, the first one provided by TCR/MHC engagement, and the second one provided by B7/CD28 interaction. Thus, neuroimmune semaphorins serve as a "signal three" for immune cell activation and regulate the overall intensity of immune response. The current knowledge on their structures, multiple receptors, specific cell/tissue/organ expression, and distinct functions in different diseases are summarized and discussed in this review.

Citing Articles

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References

Southwell A, Franciosi S, Villanueva E, Xie Y, Winter L, Veeraraghavan J . Anti-semaphorin 4D immunotherapy ameliorates neuropathology and some cognitive impairment in the YAC128 mouse model of Huntington disease. Neurobiol Dis. 2015; 76:46-56. DOI: 10.1016/j.nbd.2015.01.002. View

Chakravarti S, Sabatos C, Xiao S, Illes Z, Cha E, Sobel R . Tim-2 regulates T helper type 2 responses and autoimmunity. J Exp Med. 2005; 202(3):437-44. PMC: 2213076. DOI: 10.1084/jem.20050308. View

Serini G, Valdembri D, Zanivan S, Morterra G, Burkhardt C, Caccavari F . Class 3 semaphorins control vascular morphogenesis by inhibiting integrin function. Nature. 2003; 424(6947):391-7. DOI: 10.1038/nature01784. View

Mendez-Huergo S, Blidner A, Rabinovich G . Galectins: emerging regulatory checkpoints linking tumor immunity and angiogenesis. Curr Opin Immunol. 2017; 45:8-15. DOI: 10.1016/j.coi.2016.12.003. View

Adams R, Lohrum M, Klostermann A, Betz H, Puschel A . The chemorepulsive activity of secreted semaphorins is regulated by furin-dependent proteolytic processing. EMBO J. 1997; 16(20):6077-86. PMC: 1326291. DOI: 10.1093/emboj/16.20.6077. View

OConnor B, Eun S, Ye Z, Zozulya A, Lich J, Moore C . Semaphorin 6D regulates the late phase of CD4+ T cell primary immune responses. Proc Natl Acad Sci U S A. 2008; 105(35):13015-20. PMC: 2529027. DOI: 10.1073/pnas.0803386105. View

Elhabazi A, Delaire S, Bensussan A, Boumsell L, Bismuth G . Biological activity of soluble CD100. I. The extracellular region of CD100 is released from the surface of T lymphocytes by regulated proteolysis. J Immunol. 2001; 166(7):4341-7. DOI: 10.4049/jimmunol.166.7.4341. View

Kumanogoh A, Watanabe C, Lee I, Wang X, Shi W, Araki H . Identification of CD72 as a lymphocyte receptor for the class IV semaphorin CD100: a novel mechanism for regulating B cell signaling. Immunity. 2000; 13(5):621-31. DOI: 10.1016/s1074-7613(00)00062-5. View

van Rijn A, Paulis L, Te Riet J, Vasaturo A, Reinieren-Beeren I, van der Schaaf A . Semaphorin 7A Promotes Chemokine-Driven Dendritic Cell Migration. J Immunol. 2015; 196(1):459-68. DOI: 10.4049/jimmunol.1403096. View

10.

Kang S, Okuno T, Takegahara N, Takamatsu H, Nojima S, Kimura T . Intestinal epithelial cell-derived semaphorin 7A negatively regulates development of colitis via αvβ1 integrin. J Immunol. 2011; 188(3):1108-16. DOI: 10.4049/jimmunol.1102084. View

11.

Mine T, Harada K, Matsumoto T, Yamana H, Shirouzu K, Itoh K . CDw108 expression during T-cell development. Tissue Antigens. 2000; 55(5):429-36. DOI: 10.1034/j.1399-0039.2000.550505.x. View

12.

Esensten J, Helou Y, Chopra G, Weiss A, Bluestone J . CD28 Costimulation: From Mechanism to Therapy. Immunity. 2016; 44(5):973-88. PMC: 4932896. DOI: 10.1016/j.immuni.2016.04.020. View

13.

Zhu L, Bergmeier W, Wu J, Jiang H, Stalker T, Cieslak M . Regulated surface expression and shedding support a dual role for semaphorin 4D in platelet responses to vascular injury. Proc Natl Acad Sci U S A. 2007; 104(5):1621-6. PMC: 1785259. DOI: 10.1073/pnas.0606344104. View

14.

Herold C, Bismuth G, Bensussan A, Boumsell L . Activation signals are delivered through two distinct epitopes of CD100, a unique 150 kDa human lymphocyte surface structure previously defined by BB18 mAb. Int Immunol. 1995; 7(1):1-8. DOI: 10.1093/intimm/7.1.1. View

15.

Tang C, Gao X, Liu H, Jiang T, Zhai X . Decreased expression of SEMA3A is associated with poor prognosis in gastric carcinoma. Int J Clin Exp Pathol. 2014; 7(8):4782-94. PMC: 4152039. View

16.

Kumanogoh A, Suzuki K, Chng E, Watanabe C, Marukawa S, Takegahara N . Requirement for the lymphocyte semaphorin, CD100, in the induction of antigen-specific T cells and the maturation of dendritic cells. J Immunol. 2002; 169(3):1175-81. DOI: 10.4049/jimmunol.169.3.1175. View

17.

Neufeld G, Kessler O, Herzog Y . The interaction of Neuropilin-1 and Neuropilin-2 with tyrosine-kinase receptors for VEGF. Adv Exp Med Biol. 2003; 515:81-90. DOI: 10.1007/978-1-4615-0119-0_7. View

18.

Furuyama T, Inagaki S, Kosugi A, Noda S, Saitoh S, Ogata M . Identification of a novel transmembrane semaphorin expressed on lymphocytes. J Biol Chem. 1996; 271(52):33376-81. DOI: 10.1074/jbc.271.52.33376. View

19.

Nkyimbeng-Takwi E, Shanks K, Smith E, Iyer A, Lipsky M, DeTolla L . Neuroimmune semaphorin 4A downregulates the severity of allergic response. Mucosal Immunol. 2012; 5(4):409-19. PMC: 3378810. DOI: 10.1038/mi.2012.18. View

20.

Parkash J, Messina A, Langlet F, Cimino I, Loyens A, Mazur D . Semaphorin7A regulates neuroglial plasticity in the adult hypothalamic median eminence. Nat Commun. 2015; 6:6385. PMC: 4351556. DOI: 10.1038/ncomms7385. View