Tofacitinib treats Mycoplasma Pneumoniae Pneumonia by inhibiting the CXCR4 molecule on the CD4+ T lymphocytes

Objective: To compare the differences in CXCR4 expression on the surface of CD4 ⁺ T lymphocytes between children with severe Mycoplasma pneumoniae pneumonia (SMPP) and those with common Mycoplasma pneumoniae pneumonia (Non-SMPP) and verify in vitro the potential application value of Tofacitinib as an adjuvant therapy for MPP by affecting the CXCR4 signaling pathway. Methods: This study recruited 267 children with Mycoplasma pneumoniae pneumonia (MPP), including 42 cases of SMPP and 225 cases of Non-SMPP at Jiading District Central Hospital in Shanghai from 2023 to 2024. Laboratory tests conducted within 24 hours after admission were used as baseline data, and the differences in CD4 ⁺ CXCR4 ⁺ expression between SMPP and Non-SMPP patients were compared. Animal experiments with different medicines were performed to evaluate the mechanism and therapeutic value of Tofacitinib as an adjuvant therapy for MPP. Results: Compared with Non-SMPP, children with SMPP had more fever (p=0.0062), longer durations of hospital stays (p<0.0001), higher level of erythrocyte sedimentation rate (p=0.0161) and especial the proportion of CD4 ⁺ CXCR4 ⁺ T lymphocytes (p<0.0001).However, there were no significant differences in C-reactive protein, procalcitonin and lactate dehydrogenase levels between SMPP and Non-SMPP group. In animal experiments, compared to wild-type mice, the levels of inflammatory cytokines (IL-6, IL-8, IP-10, and IL-2) were significantly elevated in the bronchoalveolar lavage fluid (BALF) of MPP mice. Notably, the sole ligand of CXCR4, CXCL12 was also markedly increased in the BALF of MPP mice. Tofacitinib could significantly reduce the expression of CXCR4 on the surface of CD4 ⁺ cells in MPP mice, as well as decrease the expression of a series of inflammatory cytokines. Conclusion: In summary, the proportion of CD4 ⁺ CXCR4 ⁺ T cells may be served as a predictive indicator of clinical severity for the MPP. Tofacitinib can reduce the release of inflammatory cytokines by inhibiting the CXCL12/CXCR4 signaling pathway and may be used as an adjuvant therapy for MPP.