title: Impaired immunological synapse in sperm associated antigen 6 (SPAG6) deficient mice.
abstract: Sperm associated antigen 6 (SPAG6), a component of the central apparatus of the "9 + 2" axoneme, plays a central role in ciliary and flagellar motility; but, its contribution to adaptive immunity and immune system development is completely unknown. While immune cells lack a cilium, the immunological synapse is a surrogate cilium as it utilizes the same machinery as ciliogenesis including the nucleation of microtubules at the centrosome. This prompted our hypothesis that SPAG6 critically regulates the formation and function of immunological synapses. Using bone marrow reconstitution studies of adult WT mice, we demonstrate that SPAG6 is expressed in primary and secondary lymphoid tissues, is associated with the centrosome in lymphocytes, and its deficiency results in synapse disruption due to loss of centrosome polarization and actin clearance at the synaptic cleft. Improper synapse formation in Spag6KO mice was associated with defective CTL functions and impaired humoral immunity as indicated by reduced germinal centers reactions, follicular CD4 T cells, and production of class-switched antibody, together with expansion of B1 B cells. This novel report demonstrates the requirement of SPAG6 for optimal synapse formation and function, its direct role in immune cell function, and provides a novel mechanism for infertility disorders related to SPAG6.
authors.affiliation: Center for Clinical and Translational Research (CCTR), Virginia Commonwealth University, Richmond, VA 23298, USA.|Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA 23298, USA.
authors.forename: Lauren Folgosa
authors.initials: LF
authors.lastname: Cooley
authors.affiliation: Experimental Medicine and Rheumatology, William Harvey Research Institute, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK.
authors.forename: Mohey Eldin
authors.initials: ME
authors.lastname: El Shikh
authors.affiliation: Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, VA 23298, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA 23298, USA.
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Keim
authors.affiliation: Department of Infectious Diseases, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Zhengang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, VA 23298, USA.
authors.forename: Jerome F
authors.initials: JF
authors.lastname: Strauss
authors.affiliation: Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, VA 23298, USA.
authors.forename: Zhibing
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA 23298, USA.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Conrad
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000378:metabolism; D001853:Bone Marrow / Q000378:metabolism; D016923:Cell Death; D018385:Centrosome / Q000378:metabolism; D018858:Germinal Center / Q000378:metabolism; D056724:Immunity, Humoral; D054992:Immunological Synapses / Q000378:metabolism*; D008221:Lymphoid Tissue / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008868:Microtubule Proteins / Q000172:deficiency* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism; D013737:Testis / Q000378:metabolism
chemical_list: D000199:Actins; D008868:Microtubule Proteins; C504274:SPAG6 protein, mouse