Innate Type 2 Response to Aspergillus fumigatus in a Murine Model of Atopic Dermatitis–like Skin Inflammation

다국어 초록 (Multilingual Abstract)

Background: Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease mediated by T helper type 2 (Th2) cells in acute phase. Group 2 innate lymphoid cells (ILCs) play a role in the initiation of the Th2 response. Although mold exposure is associated with the development of AD, studies on the underlying mechanisms are lacking. This study investigated whether group 2 ILCs are involved in inflammation in AD-like skin induced by Aspergillus fumigatus (Af).
Methods: We investigated changes of group 2 ILCs population in Af-induced AD-like skin lesions. To induce AD-like skin lesions, Af extracts were applied to the dorsal skin of BALB/c and Rag1−/− mice five times per week, with repeat exposures at 2-week intervals.
Results: The clinical parameters were higher in the Af-treated group than in the control group. Histologic findings revealed epiderrmal and dermal thickening as well as eosinophil and mast cell infiltration into the skin of Af-treated mice. Populations of group 2 ILCs in the skin were also significantly higher in the Af-treated group. In addition, interleukin-33 mRNA expression was significantly higher in the skin lesions of the Af-treated mice. In the Rag1−/− mice lacking mature lymphocytes, AD-like skin lesions were still induced by Af and ILCs depletion using an anti-CD90.2 mAb lowered the Af-induced inflammatory response.
Conclusions: Group 2 ILCs may play a role in a murine model of Af-induced AD-like skin lesions.

참고문헌 (Reference)

• 1 Sharpe RA, "Variable risk of atopic disease due to indoor fungal exposure in NHANES 2005–2006" 45 (45): 1566-1578, 2015
• 2 Barlow JL, "Type-2 innate lymphoid cells in human allergic disease" 14 (14): 397-403, 2014
• 3 Lee HC, "Thymic stromal lymphopoietin is induced by respiratory syncytial virus-infected airway epithelial cells and promotes a type 2 response to infection" 130 (130): 1187.e5-1196.e5, 2012
• 4 Buentke E, "The allergenic yeast Malassezia furfur induces maturation of human dendritic cells" 31 (31): 1583-1593, 2001
• 5 Kim BS, "TSLP elicits IL-33-independent innate lymphoid cell responses to promote skin inflammation" 5 (5): 2013
• 6 Licona-Limón P, "TH2, allergy and group 2 innate lymphoid cells" 14 (14): 536-542, 2013
• 7 Imai Y, "Skin-specific expression of IL-33 activates group 2 innate lymphoid cells and elicits atopic dermatitis-like inflammation in mice" 110 (110): 13921-13926, 2013
• 8 Agarwal R, "Severe asthma and fungi : current evidence" 49 (49): S150-S157, 2011
• 9 Kouzaki H, "Proteases induce production of thymic stromal lymphopoietin by airway epithelial cells through protease-activated receptor-2" 183 (183): 1427-1434, 2009
• 10 Johansson C, "Positive atopy patch test reaction to Malassezia furfur in atopic dermatitis correlates with a T helper 2-like peripheral blood mononuclear cells response" 118 (118): 1044-1051, 2002
• 11 Neill DR, "Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity" 464 (464): 1367-1370, 2010
• 12 Karvonen AM, "Moisture damage and asthma : a birth cohort study" 135 (135): e598-e606, 2015
• 13 Moro K, "Innate production of T(H)2cytokines by adipose tissue-associated c-Kit+Sca-1+lymphoid cells" 463 (463): 540-544, 2010
• 14 Sonnenberg GF, "Innate lymphoid cells promote anatomical containment of lymphoid-resident commensal bacteria" 336 (336): 1321-1325, 2012
• 15 Klose CS, "Innate lymphoid cells as regulators of immunity, inflammation and tissue homeostasis" 17 (17): 765-774, 2016
• 16 Reponen T, "Infant origins of childhood asthma associated with specific molds" 130 (130): 639.e5-644.e5, 2012
• 17 Lee EB, "Increased serum thymic stromal lymphopoietin in children with atopic dermatitis" 21 (21): e457-e460, 2010
• 18 Mashiko S, "Increased frequencies of basophils, type 2 innate lymphoid cells and Th2 cells in skin of patients with atopic dermatitis but not psoriasis" 88 (88): 167-174, 2017
• 19 Nissen D, "IgE-sensitization to cellular and culture filtrates of fungal extracts in patients with atopic dermatitis" 81 (81): 247-255, 1998
• 20 Oboki K, "IL-33 is a crucial amplifier of innate rather than acquired immunity" 107 (107): 18581-18586, 2010
• 21 Fort MM, "IL-25 induces IL-4, IL-5, and IL-13 and Th2-associated pathologies in vivo" 15 (15): 985-995, 2001
• 22 Mjösberg JM, "Human IL-25-and IL-33-responsive type 2 innate lymphoid cells are defined by expression of CRTH2 and CD161" 12 (12): 1055-1062, 2011
• 23 Lee JY, "Exposure to gene-environment interactions before 1year of age may favor the development of atopic dermatitis" 157 (157): 363-371, 2012
• 24 Akei HS, "Epicutaneous aeroallergen exposure induces systemic TH2 immunity that predisposes to allergic nasal responses" 118 (118): 62-69, 2006
• 25 Platt SD, "Damp housing, mould growth, and symptomatic health state" 298 (298): 1673-1678, 1989
• 26 Roediger B, "Cutaneous immunosurveillance and regulation of inflammation by group 2 innate lymphoid cells" 14 (14): 564-573, 2013
• 27 Williams HC, "Clinical practice. Atopic dermatitis" 352 (352): 2314-2324, 2005
• 28 Leung DY, "Atopic dermatitis" 361 (361): 151-160, 2003
• 29 Jin H, "Animal models of atopic dermatitis" 129 (129): 31-40, 2009
• 30 Salimi M, "A role for IL-25 and IL-33-driven type-2 innate lymphoid cells in atopic dermatitis" 210 (210): 2939-2950, 2013