HeSReC Healthspan Research Center

Dermatology, Immunology

Autoimmunity, Tissue fibrosis, Cellular senescence, Sex difference, Personalized medicine

• Cellular senescence in autoimmune diseases, with a focus on treatment resistance and interindividual variability in therapeutic responses
• Stromal regulation of cutaneous immune responses

International

• The American Association of Immunologists

Japan

• Japanese Dermatological Association
• Japanese Society for Investigative Dermatology
• Japanese Society for Immunology
• Japanese Society of Clinical Immunology
• Japanese Society for Psoriasis Research
• Japanese Society for Vitiligo Research

Research Groups

• Hair Science Research Society of Japan

The skin is not only the organ that interfaces most directly with the external environment but also one of the tissues most profoundly affected by aging. Age-associated alterations in cellular function disrupt tissue homeostasis and are increasingly recognized as key contributors to the development, chronicity, and therapeutic resistance of many diseases, including autoimmune and fibrotic disorders. Our research focuses on skin aging from the perspectives of cellular senescence and age-associated remodeling of the tissue microenvironment, with the goal of elucidating how aging reshapes immune and fibrotic responses in the skin at the molecular level.

A particular emphasis of our work is on intractable dermatologic diseases such as alopecia areata and systemic sclerosis. We investigate how cellular senescence alters the crosstalk among immune cells, stromal cells, and tissue-resident stem cells within the skin microenvironment, and how these changes contribute to disease initiation, persistence, and variability in therapeutic responses. To address these questions, we integrate analyses of patient-derived samples—including lesional skin, serum, and peripheral blood cells—with experimental mouse models.

Our research employs state-of-the-art multi-omics approaches, including spatial transcriptomics, single-cell analyses, and metabolomics, to comprehensively characterize immune, metabolic, and neuroimmune networks operating at both local and systemic levels. By integrating these datasets, we aim to uncover the molecular mechanisms by which aging reshapes the skin microenvironment and predisposes tissues to chronic inflammation and fibrosis.

Ultimately, our goal is to translate these mechanistic insights into the identification of novel therapeutic targets and the development of innovative drug discovery strategies for aging-associated skin diseases.

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Selected Publications:

1. Segawa Y, Takahashi T, Takahashi T, Oka K, Kambayashi Y, Takahashi T, et al. Analysis of the Dynamics of Clinical Parameters and Serum Angiogenic Factors in Systemic Sclerosis Patients Undergoing Tocilizumab Treatment. Exp Dermatol. 2026;35(2):e70220.
2. Wada-Irimada M, Takahashi T, Sekine M, Okazaki T, Takahashi T, Chiba T, et al. Predictive factors for treatment responses to baricitinib in severe alopecia areata: A retrospective, multivariate analysis of 70 cases from a single center. J Dermatol. 2025;52(4):701-11.
3. Takahashi T, Stoiljkovic M, Song E, Gao XB, Yasumoto Y, Kudo E, et al. LINE-1 activation in the cerebellum drives ataxia. Neuron. 2022;110(20):3278-87 e8.
4. Takahashi T, Iwasaki A. Sex differences in immune responses. Science. 2021;371(6527):347-8.
5. Cai Y, Kim DJ, Takahashi T, Broadhurst DI, Yan H, Ma S, et al. Kynurenic acid may underlie sex-specific immune responses to COVID-19. Sci Signal. 2021;14(690).
6. Takahashi T, Ellingson MK, Wong P, Israelow B, Lucas C, Klein J, et al. Sex differences in immune responses that underlie COVID-19 disease outcomes. Nature. 2020;588(7837):315-20.