2025年林志萱及朱清良老師實驗室論文發表

The fungal protein Lingzhi-8 ameliorates psoriasis-like dermatitis in mice through gut CD103+ tolerogenic dendritic cells, retinaldehyde dehydrogenase 2, and Dectin-1

Chen-Yu Wang ¹, Jen-Yu Wang ², Yi-Yi Chou ¹, Chi-Chien Lin ³, Yu-Tsun Lin ⁴, Chi-Sheng Wu ⁵, Jr-Shiuan Lin ⁶, Ching-Liang Chu ⁷

1. Graduate Institute of Immunology, National Taiwan University College of Medicine, Taipei, Taiwan.
2. Graduate Institute of Immunology, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Dermatology, MacKay Memorial Hospital, Taipei, Taiwan; Mackay Junior College of Medicine, Nursing, and Management, New Taipei City, Taiwan; Department of Medicine, Mackay Medical College, New Taipei City, Taiwan.
3. Institute of Biomedical Sciences, National Chung-Hsing University, Taichung, Taiwan.
4. Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan.
5. Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan; Department of Otolaryngology-Head & Neck Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.
6. Graduate Institute of Immunology, National Taiwan University College of Medicine, Taipei, Taiwan. Electronic address: jrshiuanlin@ntu.edu.tw.
7. Graduate Institute of Immunology, National Taiwan University College of Medicine, Taipei, Taiwan. Electronic address: clchu01@ntu.edu.tw.

Abstract

The gut CD103+ tolerogenic dendritic cells play a key role in maintaining immune balance by inducing oral tolerance, which has been implied in reducing autoimmunity. We recently reported that the oral administration of a fungal protein Lingzhi-8 (LZ-8) prevented autoimmune colitis in mice via maintaining barrier integrity. Here, we examined the functional effect of LZ-8 on gut CD103+ DCs and on autoimmune psoriasis in a mouse model. After orally administered LZ-8 to mice, the numbers of CD103+ DCs and their retinaldehyde dehydrogenase 2 (RALDH2) activities were increased in the mesenteric lymph nodes (mLNs), which were associated with increased regulatory T cell (Treg) in the spleen and LNs. This suggests that LZ-8 induces oral tolerance by enhancing the RALDH2 activity of CD103+ DCs. In addition, the imiquimod (IMQ)-induced psoriasis-like dermatitis was attenuated in mice after LZ-8 pretreatment. In the mechanistic study, we generated gut CD103+ DC-like cells from bone marrow (BM) of wild-type mouse and cultured them in the presence of retinoic acid (RA) in vitro. We found that LZ-8 directly enhanced the RALDH2 activity of these RA-primed CD103+ DCs, which was dependent on Dectin-1 and Syk signaling pathways but not TLR4. Together, our study demonstrated that LZ-8 facilitated gut tolerogenic CD103+ DC-mediated immunosuppression by enhancing RALDH2 activity, increasing Treg cell population, and signaling through Dectin-1 and Syk. Our findings provide a novel strategy for treating psoriasis and potentially other autoimmune diseases.

Keywords: CD103(+) dendritic cell; Ling Zhi-8; Oral tolerance; Psoriasis; Regulatory T cell; Retinal dehydrogenase 2.

Biomed Pharmacother. 2025 Mar:184:117910.

doi: 10.1016/j.biopha.2025.117910.