TY - JOUR
T1 - Galectin-12 Regulates Immune Responses in the Skin through Sebaceous Glands
AU - Lin, Feng Jen
AU - Huang, Yun Hsi
AU - Tsao, Ching Han
AU - Hsieh, Wei Chen
AU - Lo, Yuan Hsin
AU - Zouboulis, Christos C.
AU - Chen, Hung Lin
AU - Liu, Fu Tong
N1 - Publisher Copyright:
© 2023 The Authors
PY - 2023/11
Y1 - 2023/11
N2 - Sebaceous glands (SGs) are holocrine glands that produce sebum, which primarily contains lipids that help to maintain the barrier function of the skin. Dysregulated lipid production contributes to the progression of some diseases characterized by dry skin, including atopic dermatitis. Although the lipid production of SGs has been well-studied, few studies have assessed their role in skin immune responses. We found that SGs and sebocytes expressed IL-4 receptor and produced high levels of T helper 2−associated inflammatory mediators after IL-4 treatment, suggesting immunomodulatory effects. Galectin-12 is a lipogenic factor expressed in sebocytes that affects their differentiation and proliferation. Using galectin-12−knockdown sebocytes, we showed that galectin-12 regulated the immune response in cells exposed to IL-4 and promoted CCL26 expression by upregulating peroxisome proliferator−activated receptor-γ. Moreover, galectin-12 suppressed the expression of endoplasmic reticulum stress−response molecules, and CCL26 upregulation by IL-4 was reversed after sebocyte treatment with inducers of endoplasmic reticulum stress, suggesting that galectin-12 controls IL-4 signaling by suppressing endoplasmic reticulum stress. Using galectin-12−knockout mice, we showed that galectin-12 positively regulated the IL-4−induced enlargement of SGs and the development of an atopic dermatitis−like phenotype. Thus, galectin-12 regulates the skin immune response by promoting peroxisome proliferator−activated receptor-γ expression and suppressing endoplasmic reticulum stress in SGs.
AB - Sebaceous glands (SGs) are holocrine glands that produce sebum, which primarily contains lipids that help to maintain the barrier function of the skin. Dysregulated lipid production contributes to the progression of some diseases characterized by dry skin, including atopic dermatitis. Although the lipid production of SGs has been well-studied, few studies have assessed their role in skin immune responses. We found that SGs and sebocytes expressed IL-4 receptor and produced high levels of T helper 2−associated inflammatory mediators after IL-4 treatment, suggesting immunomodulatory effects. Galectin-12 is a lipogenic factor expressed in sebocytes that affects their differentiation and proliferation. Using galectin-12−knockdown sebocytes, we showed that galectin-12 regulated the immune response in cells exposed to IL-4 and promoted CCL26 expression by upregulating peroxisome proliferator−activated receptor-γ. Moreover, galectin-12 suppressed the expression of endoplasmic reticulum stress−response molecules, and CCL26 upregulation by IL-4 was reversed after sebocyte treatment with inducers of endoplasmic reticulum stress, suggesting that galectin-12 controls IL-4 signaling by suppressing endoplasmic reticulum stress. Using galectin-12−knockout mice, we showed that galectin-12 positively regulated the IL-4−induced enlargement of SGs and the development of an atopic dermatitis−like phenotype. Thus, galectin-12 regulates the skin immune response by promoting peroxisome proliferator−activated receptor-γ expression and suppressing endoplasmic reticulum stress in SGs.
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U2 - 10.1016/j.jid.2023.03.1684
DO - 10.1016/j.jid.2023.03.1684
M3 - Article
C2 - 37207806
AN - SCOPUS:85162928855
SN - 0022-202X
VL - 143
SP - 2120-2131.e7
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 11
ER -