| Autor: |
Cooley LF; 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., El Shikh ME; Experimental Medicine and Rheumatology, William Harvey Research Institute, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK., Li W; Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, VA 23298, USA., Keim RC; Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA 23298, USA., Zhang Z; Department of Infectious Diseases, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China., Strauss JF; Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, VA 23298, USA., Zhang Z; Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, VA 23298, USA., Conrad DH; Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA 23298, USA. |
| Abstrakt: |
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. |
