Soluble γc receptor attenuates anti‐tumor responses of CD8 + T cells in T cell immunotherapy

et al. 2018

IJMS

Self Cite

IL-7 is an essential, nonredundant growth factor for T and B cell generation and maintenance. While IL-7 deficiency results in lymphopenia, overexpression of IL-7 can cause neoplasia in experimental models. IL-7’s involvement in neoplasia has been appreciated through studies of IL-7 transgenic (Tg) mice models and human lymphoma patients. Since we recently found that a soluble form of the common γ-chain (γc) cytokine receptor (sγc) antagonistically regulates IL-7 signaling, IL-7 and sγc double-Tg mice were generated to investigate the effects of sγc overexpression in IL-7-mediated lymphoproliferative disorders (LPDs). The overexpression of sγc prevents IL-7Tg-induced abnormal increase of LN cell numbers and the development of splenomegaly, resulting in striking amelioration of mortality and disease development. These results suggest that modification of γc cytokine responsiveness by sγc molecules might control various γc cytokine-associated hematologic malignancy, and also provide an alternative view to approach antitumor therapy.

Section: Resultssupporting

confidence: 90%

“…In previous reports, we demonstrated that sγc regulates γc cytokine signaling with the generation of sγc-overexpressing transgenic (sγcTg) mice [ 13 , 14 , 16 ]. We found with in vitro and in vivo analysis of γc cytokine responsiveness that an elevated level of sγc dramatically dampens IL-2, IL-7, and IL-15 signaling.…”

Section: Resultsmentioning

confidence: 99%

The Potential Role of a Soluble γ-Chain Cytokine Receptor as a Regulator of IL-7-Induced Lymphoproliferative Disorders

et al. 2018

IJMS

Self Cite

“…Interestingly, we observed that BT is not elevated in animals exercising even in BT water, indicating that the aquatic exercise is not strong enough to bring about changes in BT. The serum level of sγc, which is known to inhibit anti-tumor immune responses (19), decreases during tumor growth as part of its defense mechanism. The kinetics of sγc expression demonstrated are relatively late decline in housing mice compared with the exercise group (Fig.…”

Section: Resultsmentioning

confidence: 99%

Aquatic Exercise at Thermoneutral Water Temperature Enhances Antitumor Immune Responses

et al. 2019

Immune Netw

Self Cite

Despite the broad rehabilitative potential of aquatic exercises, the relationship between aquatic exercise and the immune system has not been fully elucidated to date. In particular, there are few specific and delicate immunological approaches to the effect of water temperature on immunity. Thus, we examined the effect of water temperature on immunity during aquatic exercise. The animal tumor model was adopted to examine the impact of aquatic exercise at thermoneutral temperature (TT; 29°C) on immunity compared with aquatic exercise at body temperature (BT; 36°C). Tumor-bearing mice were made to swim in TT water or in BT water for 3 wk and immune cells and their functional activity were analyzed using FACS. Tumor growth was significantly suppressed in mice that exercised in TT than in BT water. The tumor control correlated with the increased number of NK (2-fold), γδT cells (2.5-fold), NKT (2.5-fold), and cytotoxic CD8 + T cells (1.6-fold), which play a critical role in anti-tumor immune responses. Furthermore, the functional activity was dramatically improved in the TT group, showing enhanced production of IFNγ in CD8 + T cells compared with the BT group. This study demonstrates that aquatic exercise in TT water may improve protective immune responses more effectively than in BT water. Although the effects of water temperature on immune function need further verification in humans, this study suggests that water temperature in human hydrotherapy may be important for improving immune function.

“…sγc interferes with IL-2 and IL-15 signaling in CD8 + T cells (6, 35, 36). Thus, we assessed the effect of siAp8 on IL-2 or IL-15 signaling in CD8 + T cells with anti-apoptotic Bcl-2 expression (Figures 4A,B).…”

Section: Resultsmentioning

confidence: 99%

Specific Inhibition of Soluble γc Receptor Attenuates Collagen-Induced Arthritis by Modulating the Inflammatory T Cell Responses

et al. 2019

Front. Immunol.

Self Cite

IL-17 produced by Th17 cells has been implicated in the pathogenesis of rheumatoid arthritis (RA). It is important to prevent the differentiation of Th17 cells in RA. Homodimeric soluble γc (sγc) impairs IL-2 signaling and enhances Th17 differentiation. Thus, we aimed to block the functions of sγc by inhibiting the formation of homodimeric sγc. The homodimeric form of sγc was strikingly disturbed by sγc-binding DNA aptamer. Moreover, the aptamer effectively inhibited Th17 cell differentiation and restored IL-2 and IL-15 signaling impaired by sγc with evidences of increased survival of T cells. sγc was highly expressed in SF of RA patients and increased in established CIA mice. The therapeutic effect of PEG-aptamer was tested in CIA model and its treatment alleviated arthritis pathogenesis with impaired differentiation of pathogenic Th17, NKT1, and NKT17 cells in inflamed joint. Homodimeric sγc has pathogenic roles to exacerbate RA progression with differentiation of local Th17, NKT1, and NKT17 cells. Therefore, sγc is suggested as target of a therapeutic strategy for RA.