TY - JOUR
T1 - The CD40-CD40L dyad in experimental autoimmune encephalomyelitis and multiple sclerosis
AU - Aarts, Suzanne A.B.M.
AU - Seijkens, Tom T.P.
AU - van Dorst, Koos J.F.
AU - Dijkstra, Christine D.
AU - Kooij, Gijs
AU - Lutgens, Esther
N1 - Publisher Copyright:
© 2017 Aarts, Seijkens, van Dorst, Dijkstra, Kooij and Lutgens.
PY - 2017/12/12
Y1 - 2017/12/12
N2 - The CD40-CD40L dyad is an immune checkpoint regulator that promotes both innate and adaptive immune responses and has therefore an essential role in the development of inflammatory diseases, including multiple sclerosis (MS). In MS, CD40 and CD40L are expressed on immune cells present in blood and lymphoid organs, affected resident central nervous system (CNS) cells, and inflammatory cells that have infiltrated the CNS. CD40-CD40L interactions fuel the inflammatory response underlying MS, and both genetic deficiency and antibody-mediated inhibition of the CD40-CD40L dyad reduce disease severity in experimental autoimmune encephalomyelitis (EAE). Both proteins are therefore attractive therapeutic candidates to modulate aberrant inflammatory responses in MS. Here, we discuss the genetic, experimental and clinical studies on the role of CD40 and CD40L interactions in EAE and MS and we explore novel approaches to therapeutically target this dyad to combat neuroinflammatory diseases.
AB - The CD40-CD40L dyad is an immune checkpoint regulator that promotes both innate and adaptive immune responses and has therefore an essential role in the development of inflammatory diseases, including multiple sclerosis (MS). In MS, CD40 and CD40L are expressed on immune cells present in blood and lymphoid organs, affected resident central nervous system (CNS) cells, and inflammatory cells that have infiltrated the CNS. CD40-CD40L interactions fuel the inflammatory response underlying MS, and both genetic deficiency and antibody-mediated inhibition of the CD40-CD40L dyad reduce disease severity in experimental autoimmune encephalomyelitis (EAE). Both proteins are therefore attractive therapeutic candidates to modulate aberrant inflammatory responses in MS. Here, we discuss the genetic, experimental and clinical studies on the role of CD40 and CD40L interactions in EAE and MS and we explore novel approaches to therapeutically target this dyad to combat neuroinflammatory diseases.
KW - CD40
KW - CD40L
KW - Experimental autoimmune encephalomyelitis
KW - Inflammation
KW - Multiple sclerosis
KW - Tumor necrosis factor receptor-associated factors
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U2 - 10.3389/fimmu.2017.01791
DO - 10.3389/fimmu.2017.01791
M3 - Review article
AN - SCOPUS:85038005742
SN - 1664-3224
VL - 8
JO - Frontiers in immunology
JF - Frontiers in immunology
IS - DEC
M1 - 1791
ER -