ULK Regulates The Function Of CD4~+ T Cells And Immune Responses

The immune system is classified into innate immunity and acquired immunity,and the latter can be divided into T cell-mediated cellular immune response and B cell-mediated humoral immune response.Humoral immunity is an immune mechanism for B cells to produce antibodies for protection purposes.Cell immunity is an immune response that is dominated by T cell responses.After antigen stimulation,T cells proliferate and differentiate to form effector T cells,mainly including cytotoxic T cells and helper T cells.However humoral immunity and cellular immunity complement each other and are indispensable because B cells need to be activated and differentiated in the germinal center(GC),activated B cells can differentiate into plasma cells which secrete high-affinity antibodies and memory B cells both with the help of TFH cells.Therefore,the study of the differentiation and function of CD4+ T cells to TFH cells and the formation of immune memory provides an important theoretical basis for humoral immune responses.Since the Belgian scientist Christian de Duve proposed the concept of"autophagy" at the 1963 lysosomal international conference,autophagy has become the most popular research direction after apoptosis.An Japanese scientists discovered and elucidated mechanisms underlying autophagy and was awarded the 2016 Nobel Prize in Physiology and Medicine.Current research shows that the ULK gene can initiate the process of autophagy under stress.Autophagy also plays an important role in the occurrence of diseases such as cancer,neurodegenerative diseases,immune inflammation,and rheumatism.Therefore,the relationship between the study about ULK gene and cellular autophagy provides a theoretical basis and a new therapeutic target for the treatment of these diseases.However,there are few reports on the role and mechanism of ULK genes in the immune system.These papers initially explore whether ULK regulates the immune response of CD4+ T cells and further explores how it regulates the immune response of CD4+ T cells.We used LCMV and OVA/Alum/LPS to immunize the ULK conditional knockout mice to investigate whether the immune response of CD4+ T cells after ULK knockout was affected.The results show that the absence of ULK affects the activation of CD4+ T cells,but does not affect the differentiation,germinal center reaction,and plasma cell(PC)differentiation.We hypothesize may be that the immunogenic effect is saturated therefore mask the difference.We have also used cell adoptive transfer model and NP-OVA/Alum immunization to study the effect of ULK gene on the differentiation and function of CD4+ T cells.The results showed that the proliferation of CD4+ T cells was inhibited ULK deletion,while the differentiation of TFH cells increased significantly,and the production of high affinity antibodies also increased accordingly.In summary,we conclude that the deletion of ULK 1/2 may inhibit the activation and proliferation of CD4+ T cells,but it promotes the differentiation of TFH cells,and the production of high-affinity antibodies,thus regulating the immune response of CD4+ T cells.