Although immobility is a common cause of muscle atrophy, the mechanism underlying this causality is unclear. We here show that Krüppel-like factor 15 (KLF15) and IL-6 are upregulated in skeletal muscle of limb-immobilized mice and that mice with KLF15 deficiency in skeletal muscle or with systemic IL-6 deficiency are protected from immobility-induced muscle atrophy. A newly developed Ca²⁺ bioimaging revealed that the cytosolic Ca²⁺ concentration ([Ca²⁺]_i) of skeletal muscle is reduced to below the basal level by immobilization, which is associated with the downregulation of Piezo1. Acute disruption of Piezo1 in skeletal muscle induced Klf15 and Il6 expression as well as muscle atrophy, which was prevented by antibodies against IL-6. A role for the Piezo1/KLF15/IL-6 axis in immobility-induced muscle atrophy was validated in human samples. Our results thus uncover a paradigm for Ca²⁺ signaling in that a decrease in [Ca²⁺]_i from the basal level triggers a defined biological event.

Upregulation of N-type Ca ²⁺ channel dependent subunits increases functional connections and synchronization for pain formation.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a type of autoimmune encephalitis that can be paraneoplastic and usually responds to tumor resection and immunotherapy. More than 75% of patients with anti-NMDAR encephalitis fully recover or have only mild sequelae, whereas the remainder experience severe disability. It remains unknown why certain cases have refractory clinical disease courses. We report a case of anti-NMDAR encephalitis with bilateral ovarian teratomas who was refractory to tumor resection and early initiation of immunotherapy. During intensive care, immunohistochemical analyses of her cerebrospinal fluid showed persistently high reactivity of NMDAR antibody over time. Six months after the operation, pelvic computed tomography detected a recurrent ovarian teratoma. After total enucleation of the bilateral ovaries, with significant pathological findings of bilateral mature cystic teratomas, her clinical condition improved rapidly, paralleled by a decrease in anti-NMDAR reactivity. This case illustrates the need to keep considering why extensive treatment fails to influence the disease when we encounter patients with refractory anti-NMDAR encephalitis. Failure to improve after ovarian resection could be a marker of recurrent ovarian teratoma in anti-NMDAR encephalitis.