Arf1 and Arf6 Synergistically Maintain Survival of T Cells during Activation
| Autor: | Yuki Ikuta, Yasunori Kanaho, Satoshi Matsuda, Madoka Ozawa, Kana Bando, Yui Kotani, Mami Sumiyoshi, Takaya Abe, Kazutomo Suzue, Shigeo Koyasu, Tomoya Katakai, Toshio Watanabe, Taketo Yamada |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Encephalomyelitis
Autoimmune Experimental Cell Survival T-Lymphocytes T cell Immunology Receptors Antigen T-Cell Apoptosis Mice Transgenic Biology Lymphocyte Activation Mice Immune system medicine Animals Immunology and Allergy Cells Cultured ADP-Ribosylation Factors T-cell receptor Experimental autoimmune encephalomyelitis Colitis medicine.disease Cell biology Mice Inbred C57BL medicine.anatomical_structure Proto-Oncogene Proteins c-bcl-2 ADP-Ribosylation Factor 6 ADP-Ribosylation Factor 1 Cytokine secretion Immunotherapy Guanine nucleotide exchange factor Ras superfamily Signal Transduction |
| Zdroj: | The Journal of Immunology. 206:366-375 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.2000971 |
| Popis: | ADP-ribosylation factor (Arf) family consisting of six family members, Arf1–Arf6, belongs to Ras superfamily and orchestrates vesicle trafficking under the control of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins. It is well established that brefeldin A, a potent inhibitor of ArfGEFs, blocks cytokine secretion from activated T cells, suggesting that the Arf pathway plays important roles in T cell functions. In this study, because Arf1 and Arf6 are the best-characterized members among Arf family, we established T lineage–specific Arf1-deficient, Arf6-deficient, and Arf1/6 double-deficient mice to understand physiological roles of the Arf pathway in the immune system. Contrary to our expectation, Arf deficiency had little or no impact on cytokine secretion from the activated T cells. In contrast, the lack of both Arf1 and Arf6, but neither Arf1 nor Arf6 deficiency alone, rendered naive T cells susceptible to apoptosis upon TCR stimulation because of imbalanced expression of Bcl-2 family members. We further demonstrate that Arf1/6 deficiency in T cells alleviates autoimmune diseases like colitis and experimental autoimmune encephalomyelitis, whereas Ab response under Th2-polarizing conditions is seemingly normal. Our findings reveal an unexpected role for the Arf pathway in the survival of T cells during TCR-induced activation and its potential as a therapeutic target in the autoimmune diseases. |
| Databáze: | OpenAIRE |
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