Stage-dependent immunity orchestrates AQP4 antibody-guided NMOSD pathology: a role for netting neutrophils with resident memory T cells in situ.

Autor: Nakajima A; Department of Neurology, Brain Research Institute, Niigata University, 1-757 Asahimachi, Chuo-Ku, Niigata, 951-8585, Japan., Yanagimura F; Department of Neurology, Brain Research Institute, Niigata University, 1-757 Asahimachi, Chuo-Ku, Niigata, 951-8585, Japan.; Department of Neurology, NHO Niigata National Hospital, 3-52 Akasakamachi, Kashiwazaki, Niigata, 945-8585, Japan., Saji E; Department of Neurology, Brain Research Institute, Niigata University, 1-757 Asahimachi, Chuo-Ku, Niigata, 951-8585, Japan., Shimizu H; Department of Pathology, Brain Research Institute, Niigata University, 1-757 Asahimachi, Chuo-Ku, Niigata, 951-8585, Japan., Toyoshima Y; Department of Pathology, Brain Research Institute, Niigata University, 1-757 Asahimachi, Chuo-Ku, Niigata, 951-8585, Japan.; Department of Neurology, Brain Disease Center, Agano Hospital, 6317-15 Yasuda, Agano, Niigata, 959-2221, Japan., Yanagawa K; Department of Neurology, Brain Research Institute, Niigata University, 1-757 Asahimachi, Chuo-Ku, Niigata, 951-8585, Japan., Arakawa M; Department of Neurology, Brain Research Institute, Niigata University, 1-757 Asahimachi, Chuo-Ku, Niigata, 951-8585, Japan.; Musashi Clinic, 20-1 Hakusanura 2, Chuo-Ku, Niigata, 951-8131, Japan., Hokari M; Department of Neurology, Brain Research Institute, Niigata University, 1-757 Asahimachi, Chuo-Ku, Niigata, 951-8585, Japan., Yokoseki A; Department of Neurology, Brain Research Institute, Niigata University, 1-757 Asahimachi, Chuo-Ku, Niigata, 951-8585, Japan.; Department of Neurology, Niigata Medical Center, 27-11 Kobari 3, Nishi-Ku, Niigata, 950-2022, Japan., Wakasugi T; Department of Neurology, Brain Research Institute, Niigata University, 1-757 Asahimachi, Chuo-Ku, Niigata, 951-8585, Japan.; Department of Neurology, NHO Nishiniigata Chuo Hospital, 14-1 Masago 1, Nishi-Ku, Niigata, 950-2085, Japan., Okamoto K; Department of Neurosurgery, Brain Research Institute, Niigata University, 1-757 Asahimachi, Chuo-Ku, Niigata, 951-8585, Japan., Takebayashi H; Division of Neurobiology and Anatomy, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachi, Chuo-Ku, Niigata, 951-8510, Japan., Fujii C; Department of Neurology, Kansai Medical University Medical Center, 10-15 Fumizonocho, Moriguchi, Osaka, 570-8507, Japan.; Department of Neurology, Graduate School of Medical Sciences, Kyoto Prefectural University of Medicine, 465 Kajii-Cho, Kawaramachi-Hirokoji, Kamigyo-Ku, Kyoto, 602-8566, Japan., Itoh K; Department of Pathology and Applied Neurobiology, Graduate School of Medical Sciences, Kyoto Prefectural University of Medicine, 465 Kajii-Cho, Kawaramachi-Hirokoji, Kamigyo-Ku, Kyoto, 602-8566, Japan., Takei YI; Department of Neurology, NHO Matsumoto Medical Center, 2-20-30 Muraimachi-Minami, Matsumoto, Nagano, 399-8701, Japan., Ohara S; Department of Neurology, NHO Matsumoto Medical Center, 2-20-30 Muraimachi-Minami, Matsumoto, Nagano, 399-8701, Japan.; Department of Neurology, Iida Hospital, 1-15 Odori, Iida, Nagano, 395-8505, Japan., Yamada M; Department of Brain Disease Research, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan., Takahashi H; Department of Pathology, Brain Research Institute, Niigata University, 1-757 Asahimachi, Chuo-Ku, Niigata, 951-8585, Japan.; Department of Pathology and Laboratory Medicine, Niigata Neurosurgical Hospital, 3057 Yamada, Nishi-Ku, Niigata, 950-1101, Japan., Nishizawa M; Department of Neurology, Brain Research Institute, Niigata University, 1-757 Asahimachi, Chuo-Ku, Niigata, 951-8585, Japan.; Niigata University of Health and Welfare, 1398 Shimami-Cho, Kita-Ku, Niigata, 950-3198, Japan., Igarashi H; Center for Integrated Human Brain Science, Brain Research Institute, Niigata University, 1-757 Asahimachi, Chuo-Ku, Niigata, 951-8585, Japan., Kakita A; Department of Pathology, Brain Research Institute, Niigata University, 1-757 Asahimachi, Chuo-Ku, Niigata, 951-8585, Japan., Onodera O; Department of Neurology, Brain Research Institute, Niigata University, 1-757 Asahimachi, Chuo-Ku, Niigata, 951-8585, Japan., Kawachi I; Department of Neurology, Brain Research Institute, Niigata University, 1-757 Asahimachi, Chuo-Ku, Niigata, 951-8585, Japan. ikawachi@bri.niigata-u.ac.jp.; Medical Education Center, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachi, Chuo-Ku, Niigata, 951-8510, Japan. ikawachi@bri.niigata-u.ac.jp.
Jazyk: angličtina
Zdroj: Acta neuropathologica [Acta Neuropathol] 2024 Apr 24; Vol. 147 (1), pp. 76. Date of Electronic Publication: 2024 Apr 24.
DOI: 10.1007/s00401-024-02725-x
Abstrakt: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease of the CNS characterized by the production of disease-specific autoantibodies against aquaporin-4 (AQP4) water channels. Animal model studies suggest that anti-AQP4 antibodies cause a loss of AQP4-expressing astrocytes, primarily via complement-dependent cytotoxicity. Nonetheless, several aspects of the disease remain unclear, including: how anti-AQP4 antibodies cross the blood-brain barrier from the periphery to the CNS; how NMOSD expands into longitudinally extensive transverse myelitis or optic neuritis; how multiphasic courses occur; and how to prevent attacks without depleting circulating anti-AQP4 antibodies, especially when employing B-cell-depleting therapies. To address these knowledge gaps, we conducted a comprehensive 'stage-dependent' investigation of immune cell elements in situ in human NMOSD lesions, based on neuropathological techniques for autopsied/biopsied CNS materials. The present study provided three major findings. First, activated or netting neutrophils and melanoma cell adhesion molecule-positive (MCAM + ) helper T (T H ) 17/cytotoxic T (T C ) 17 cells are prominent, and the numbers of these correlate with the size of NMOSD lesions in the initial or early-active stages. Second, forkhead box P3-positive (FOXP3 + ) regulatory T (T reg ) cells are recruited to NMOSD lesions during the initial, early-active or late-active stages, suggesting rapid suppression of proinflammatory autoimmune events in the active stages of NMOSD. Third, compartmentalized resident memory immune cells, including CD103 + tissue-resident memory T (T RM ) cells with long-lasting inflammatory potential, are detected under "standby" conditions in all stages. Furthermore, CD103 + T RM cells express high levels of granzyme B/perforin-1 in the initial or early-active stages of NMOSD in situ. We infer that stage-dependent compartmentalized immune traits orchestrate the pathology of anti-AQP4 antibody-guided NMOSD in situ. Our work further suggests that targeting activated/netting neutrophils, MCAM + T H 17/T C 17 cells, and CD103 + T RM cells, as well as promoting the expansion of FOXP3 + T reg cells, may be effective in treating and preventing relapses of NMOSD.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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