Expression of CD226 is upregulated on Tr1 cells from neuromyelitis optica spectrum disorder patients

“…highly immune-suppressive subsets of CD4+ T cells, and they exert important suppressive and homeostasis effects on cancer, autoimmune disorders, and inflammatory responses (Jia et al., 2019; Josefowicz et al., 2012; Kleinewietfeld & Hafler, 2014; Roncarolo et al., 2014, 2018; Zeng et al., 2015).”

“Regulatory T cells are mainly Foxp3+ Treg cells and Foxp3– Tr1 cells (Sakaguchi et al., 2010; Zeng et al., 2015).”

“NMOSD patients had lower number of Tr1 cells (CD4+CD49b+CD223+) (Gagliani et al., 2013), and Tr1 cells/CD4+ T cells ratio was also reduced (Figure 2a,b).”

“Brain and Behavior published byWiley Periodicals LLC. typic continuumof primarily immune-mediated astrocyte injury, rather than a primary demyelinating disease, with preferential involvement of the optic nerves, brainstem, and the spinal cord (de Seze et al., 2016; Franciotta et al., 2017).”

“…highly immune-suppressive subsets of CD4+ T cells, and they exert important suppressive and homeostasis effects on cancer, autoimmune disorders, and inflammatory responses (Jia et al., 2019; Josefowicz et al., 2012; Kleinewietfeld & Hafler, 2014; Roncarolo et al., 2014, 2018; Zeng et al., 2015).”

“It has recently become appreciated that CD226 might be involved in functions of regulatory T cells (Fourcade et al., 2018; Fuhrman et al., 2015; Mu et al., 2020; Wang et al., 2019).”

“…highly immune-suppressive subsets of CD4+ T cells, and they exert important suppressive and homeostasis effects on cancer, autoimmune disorders, and inflammatory responses (Jia et al., 2019; Josefowicz et al., 2012; Kleinewietfeld & Hafler, 2014; Roncarolo et al., 2014, 2018; Zeng et al., 2015).”

“Regulatory T cells are mainly Foxp3+ Treg cells and Foxp3– Tr1 cells (Sakaguchi et al., 2010; Zeng et al., 2015).”

“Considering previous findings reporting the number of Tr1 cells was decreased, and the activity of Tr1 cells for secreting IL-10 was also impaired in MS patients, MS monkeys, and mouse EAE model by multiple mechanisms (Astier & Hafler, 2007; Ma et al., 2009; Martinez-Forero et al., 2008), we found both Tr1 and Treg ce…”

“There was no controversy over AQP4-antibody-seropositive NMOSD, but alternative diagnoses were required with AQP4-antibodyseronegative (Fujihara, 2019; Jurynczyk et al., 2017).”

“CD226, an important costimulatory molecule for T cells, is widely involved in the regulation of immune cells, such as the differentiation and effector function of initial T cells and the polarization and effector functions of Th1 cells (Dardalhon et al., 2005; Sherrington et al., 1997).”

“…Tr1 cells was decreased, and the activity of Tr1 cells for secreting IL-10 was also impaired in MS patients, MS monkeys, and mouse EAE model by multiple mechanisms (Astier & Hafler, 2007; Ma et al., 2009; Martinez-Forero et al., 2008), we found both Tr1 and Treg cells decreased in NMOSD patients.”

“…Tr1 cells was decreased, and the activity of Tr1 cells for secreting IL-10 was also impaired in MS patients, MS monkeys, and mouse EAE model by multiple mechanisms (Astier & Hafler, 2007; Ma et al., 2009; Martinez-Forero et al., 2008), we found both Tr1 and Treg cells decreased in NMOSD patients.”

“…Tr1 cells was decreased, and the activity of Tr1 cells for secreting IL-10 was also impaired in MS patients, MS monkeys, and mouse EAE model by multiple mechanisms (Astier & Hafler, 2007; Ma et al., 2009; Martinez-Forero et al., 2008), we found both Tr1 and Treg cells decreased in NMOSD patients.”

“Brain and Behavior published byWiley Periodicals LLC. typic continuumof primarily immune-mediated astrocyte injury, rather than a primary demyelinating disease, with preferential involvement of the optic nerves, brainstem, and the spinal cord (de Seze et al., 2016; Franciotta et al., 2017).”

“CD226 is an immunoglobulin-like molecule expressed in hematopoietic cells such as T cells, NK cells, a subset of B cells, mono- cytes/macrophages, and platelets in human (Castriconi et al., 2004; Li et al., 2020; Nagayama-Hasegawa et al., 2019; Sherrington et al., 1997; Vo et al., 2016).”

“CD226 is an immunoglobulin-like molecule expressed in hematopoietic cells such as T cells, NK cells, a subset of B cells, mono- cytes/macrophages, and platelets in human (Castriconi et al., 2004; Li et al., 2020; Nagayama-Hasegawa et al., 2019; Sherrington et al., 1997; Vo et al., 2016).”

“CD226 is an immunoglobulin-like molecule expressed in hematopoietic cells such as T cells, NK cells, a subset of B cells, mono- cytes/macrophages, and platelets in human (Castriconi et al., 2004; Li et al., 2020; Nagayama-Hasegawa et al., 2019; Sherrington et al., 1997; Vo et al., 2016).”

“It has recently become appreciated that CD226 might be involved in functions of regulatory T cells (Fourcade et al., 2018; Fuhrman et al., 2015; Mu et al., 2020; Wang et al., 2019).”

“Our laboratory has previously shown that CD226 polyclonal antibody treatment of EAE mice has reduced symptoms and susceptibility by promoted IL-10 production (Zhang et al., 2016).”

“…highly immune-suppressive subsets of CD4+ T cells, and they exert important suppressive and homeostasis effects on cancer, autoimmune disorders, and inflammatory responses (Jia et al., 2019; Josefowicz et al., 2012; Kleinewietfeld & Hafler, 2014; Roncarolo et al., 2014, 2018; Zeng et al., 2015).”

“In neuromyelitis optica, CD226 overexpression on T regulatory type 1 cells correlates with disease severity, suggesting its role as a progression biomarker [106].”

“We recently reported increased levels of sCD226 in the serum of patients with MS and NMOSD (54).”