Experimental autoimmune breast failure: a model for lactation insufficiency, postnatal nutritional deprivation, and prophylactic breast cancer vaccination.
Mastitis is a substantial clinical problem in lactating women that may result in severe pain and abrupt termination of breastfeeding, thereby predisposing infants to long-term health risks. Many cases of mastitis involve no known infectious agent and may fundamentally be due to autoimmune-mediated inflammation of the breast. Herein, we develop a murine model of autoimmune mastitis and provide a detailed characterization of its resulting phenotype of breast failure and lactation insufficiency. To generate breast-specific autoimmunity, we immunized SWXJ mice with recombinant mouse α-lactalbumin, a lactation-dependent, breast-specific differentiation protein critical for production of lactose. Mice immunized with α-lactalbumin showed extensive T-cell-mediated inflammation in lactating normal breast parenchyma but none in nonlactating normal breast parenchyma. This targeted autoimmune attack resulted in breast failure characterized by lactation insufficiency and decreased ability to nurture offspring. Although immunization with α-lactalbumin had no effect on fertility and birth numbers, pups nursed by α-lactalbumin-immunized mice showed significantly disrupted growth often accompanied by kwashiorkor-like nutritional abnormalities, including alopecia, liver toxicity, and runting. This experimental model of autoimmune breast failure has useful applications for prophylactic breast cancer vaccination and for addressing inflammatory complications during breastfeeding. In addition, this model is suited for investigating nutritionally based "failure-to-thrive" issues, particularly regarding the long-term implications of postnatal nutritional deprivation.
Department of Immunology, Lerner Research Institute, Cleveland Clinic, Ohio 44195, USA.
Pavani
P
Kesaraju
Ritika
R
Jaini
Justin M
JM
Johnson
Cengiz Z
CZ
Altuntas
Jessica J
JJ
Gruden
Cagri
C
Sakalar
Vincent K
VK
Tuohy
D000818:Animals; D000831:Animals, Newborn; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D017252:CD3 Complex / Q000378:metabolism; D019496:Cancer Vaccines / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D045142:Cross-Priming / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D007109:Immunity / Q000276:immunology; D007116:Immunization, Passive; D007249:Inflammation / Q000150:complications / Q000276:immunology / Q000473:pathology; D007768:Lactalbumin / Q000276:immunology; D007774:Lactation / Q000235:genetics / Q000502:physiology*; D008321:Mammary Glands, Animal / Q000276:immunology* / Q000473:pathology*; D008325:Mammary Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D009747:Nutritional Physiological Phenomena; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination
D017252:CD3 Complex; D019496:Cancer Vaccines; D007768:Lactalbumin