Semaphorin 7A is a negative regulator of T cell responses.
Semaphorins play an essential role in axonal guidance, and emerging evidence points to diverse functions of several Semaphorin family members in the immune system. Semaphorin 7A (Sema7A) promotes axonal growth in the central nervous system. Here, we show that Sema7A also plays a critical role in negative regulation of T cell activation and function. T cells deficient in Sema7A exhibit enhanced homeostatic and antigen-induced proliferative response. Moreover, autoreactive Sema7A-deficient T cells mediate aggressive autoimmune disease. The deficiency in Sema7A leads to defective TCR downmodulation and T cell hyperresponsiveness. These results demonstrate an important role of Sema7A in limiting autoimmune responses and add to growing evidence of shared signaling pathways used by the immune and nervous systems.
Czopik
Agnieszka K
AK
Section of Immunobiology, Yale University, New Haven, Connecticut 06520, USA.
Bynoe
Margaret S
MS
Palm
Noah
N
Raine
Cedric S
CS
Medzhitov
Ruslan
R
D019264:Adoptive Transfer; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology* / Q000378:metabolism; D015551:Autoimmunity; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D058851:GPI-Linked Proteins; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000473:pathology; D007150:Immunohistochemistry; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D039961:Semaphorins / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D015703:Antigens, CD; D058851:GPI-Linked Proteins; D011948:Receptors, Antigen, T-Cell; C118753:SEMA7A protein, human; D039961:Semaphorins