Intestinal Immunology

Goal: My laboratory has explored the immune mechanism involved in mucosal defense, which has the potential to open new avenues to prevent or treat many diseases such as inflammatory bowel disease, allergy, obesity, autism, atherosclerosis, and cancer. In addition to research activity, I have served as Editorial Board members in Gastroenterology, Journal of Immunology, and Journal of Gastroenterology.
IL-22: An IL-10 cytokine family, IL-22 serves as a specific activator of epithelial defense through signal transducer and activator of transcriptions (STAT) 3. My laboratory has identified the therapeutic potential of IL-22 and its downstream molecule Mucin1 in murine models of IBD (J Clin Invest 2008:534, Gastroenterology 2012:865). The importance of this finding from mice is highlighted by recent human genetic studies identifying IL-22 and its associated molecules as IBD susceptibility genes. In addition, epithelial defense, which is required for maintaining appropriate host/microbial interaction, is considered to play an important role in suppressing many disease conditions such as allergy, autoimmune diseases, cancer, obesity, and autism.

Breg: My laboratory, in collaboration with Dr. Atul Bhan, previously identified a regulatory B cell subset we have termed Breg, which produces large amounts of IL-10 and improves ongoing intestinal inflammation (Immunity 2002: 219, J Immunol 2006:705). The last five years have seen enormous progress in this area. Breg has now been confirmed to exist in diverse inflammatory conditions ranging from IBD to GVHD. My laboratory has recently expanded our initial observations to the discovery of an alternative pathway of B cell maturation in the intestine that gives rise to a tissue-specific B cell subset that we believe serves as a major player in mucosal defense (J Exp Med 2008:1357). We are currently studying how these unique intestinal B cells differentiate into Breg and whether the cell-based therapy utilizing Breg is applicable for many disease conditions.

Tissue-specific and cell-specific therapy: Over one million patients each year are newly diagnosed with digestive diseases, such as IBD and colorectal cancer. Digestive tract is easily accessible by endoscopy for diagnosis and therapy. In collaboration with Dr. Andy Yun, Harvard Medical School we have developed an endoscopic optical image-guided immobile-cell delivery system that can non-invasively make an in vivo diagnosis of digestive diseases at the microscopic resolution (Nat Method 2010:303) and can simultaneously perform the tissue-specific and cell-specific biological therapy through immobile cell- and mesenchimal stem cell-mediated gene delivery systems that are designed to specifically targets either, but not both, of adaptive or innate immune cells. In addition, we have discovered that colitogenic CD4+ T cells express unique core-1 O-glycan that may be targeted for cell-specific therapy (Immunity 2004:681, J Exp Med 2012:2383).


目的: 腸管内には、重さにして1.5kg以上もの、これまでの想像をはるかに超えた種類の微生物が存在する事が近年明らかにされた。これらの微生物に対する正常な生体反応が保てなくなると、腸管局所の病気である炎症性腸疾患や大腸癌のみならず、ある種の自己免疫疾患、アレルギー疾患、肥満、自閉症等の発症にも関与する事が近年報告され始めている。 当講座では、遺伝子操作マウス(J Pathol 2016:205)とヒト検体を用いた基礎・臨床の両面的研究を介して、これらの疾患の予防及び治療のための「おなかの健康免疫」戦略の開発を目的とする。 これまでの業績は、このページの下部に示す。

インターロイキン22 腸管の微生物に対して第一の防御を担うのが腸上皮細胞である。 我々は、インターロイキン22(IL-22) と呼ばれるサイトカインと、その下流分子であるMucin1が腸上皮細胞の防御に重要な役割を担う事を報告している (J Clin Invest 2008:534, Gastroenterology 2012:865)。 また、IL-22に関与する多くの分子が炎症性腸疾患(IBD)の感受性遺伝子としても近年同定されると共に、IL-22が幹細胞傷害の抑制にも寄与している事が近年同定されている。 よって、このIL-22系列機構の解明は、IBDに対する新たな治療法の開発のみならず、再生医療においても多大な光明をもたらす事が期待される。しかしながら、IL-22のあまりに複雑な役割も近年明らかになりつつある。例えば、IL-22はある時は炎症に対し抑制因子として作用するも、異なった環境下では、むしろ病的作用を発揮する。 よって、この様なIL-22の正反対の作用を生み出す機序を解明できれば、IL-22関連療法の開発に光明をもたらす事が期待される。

Breg細胞: B細胞は抗体を産生する事によりのみ免疫機能を掌ると、これまで長く考えられていた。 しかし、我々は調節性サイトカインであるIL-10を産生する事によりマウスの実験腸炎を改善できるB細胞群を同定し、Regulatory B cells (Breg)と命名した(Immunity 2002:219, J Immunol 2006:705)。その後、IL-10を産生できるB細胞群は、炎症性腸疾患、自己免疫疾患、アレルギー、移植免疫、感染性疾患、ガン免疫、肥満及び動脈硬化等の多くの疾患に対して抑制的に働いている事が近年明らかになってきている。また、我々は腸管内にはIL-12を介して、微生物に対する免疫防御を活性化するB細胞群も存在する事も同定している(J Exp Med 2008:1357)。 よって、これらのサイトカイン産生、特に免疫抑制サイトカインIL-10産生B細研究の更なる発展は、種々の疾患に対する新たな細胞療法の開発に光明をもたらす事が期待される。2014年に米国ハーバード大学医学部より本学に着任後、日本学術振興会からの研究活動スタート支援及び基盤研究(B)の助成を受けて、日本において制御性B細胞研究の更なる発展のための研究は進展中である。

細胞特異的組織特異的治療法: 現在我々の体内には、機能的に異なる多大な種類の免疫細胞が存在する事が明らかになっている。例えば、CD4陽性T細胞は少なくとも10種類以上の機能的に異なる細胞群に分類され、疾患に依存して善玉または悪玉として働く事ができる。よって、悪玉となるCD4陽性T細胞のみを特異的に標的とする事ができる細胞特異的療法は、病気をより効果的に、そしてより安全に治療するために多大な貢献をきたす事が期待される。我々は、腸管の悪玉CD4陽性T細胞は特殊な糖鎖構造を細胞表面に発現している事を同定している(Immunity 2004:681, J Exp Med 2012:2383)。よって、この糖鎖構造を標的とした、悪玉CD4陽性T細胞特異的治療法の開発を試みる。 また、マウスの大腸特異的遺伝子治療法を開発すると共に(J Clin Invest 2008:534)、非侵襲的に組織学的診断が可能な内視鏡を開発し(Nat Method 2010:303)、種々の消化管疾患に対する腸特異的・細胞特異的治療法の確立を目標とする。

公的貢献:これまで、アメリカ免疫学会機関紙Journal of ImmunologyのAssociate Editor, アメリカ消化器病学会機関紙GasteroenterologyのEditorial Board、日本消化器病学会機関紙Journal of GastroenterologyのAssociate Editorをはじめ、多くの論文の査読員、欧米諸国の数々の研究助成金審査委員を務めてきた。 これらの経験を基に、世界に認められる医学研究の探求を目標とする。:



久留米大学医学部に着任後の業績 (February 2014 ~ )

Pyzik M, Rath T, Kuo TT, Win S, Baker K, Hubbard JJ, Grenha R, Gandhi A, Krämer TD, Mezo AR, Taylor ZS, McDonnell K, Nienaber V, Andersen JT, Mizoguchi A, Blumberg L, Purohit S, Jones SD, Christianson G, Lencer WI, Sandlie I, Kaplowitz N, Roopenian DC, Blumberg RS.  Hepatic FcRn regulates albumin homeostasis and susceptibility to liver injury. Proc Natl Acad Sci U S A. 2017, 114:E2862-E2871

Mizoguchi A. A novel intestinal organoid-based in vitro co-culture system to dissect out the initial host defense system. J Gastroenterol. 2017, 52:123-124

Caballero-Franco C, Guma M, Choo M-K, Sano Y, Enzler T, Karin M, Mizoguchi A, and Park JM.  Epithelial control of gut-associated lymphoid tissue formation through p38α-dependent restraint of NF-κB signaling. J Immunol, 2016, 196:2368-2376

Mizoguchi A, Takeuchi T, Himuro H, Okada T, and Mizoguchi E. Genetically engineered mouse models of IBD. J Pathol 2016, 238: 205-219

DeGruttola AK, Low D,  Mizoguchi A, and Mizoguchi E.  Current understanding of dysbiosis in disease in human and animal models. Inflammatory Bowel Disease 2016, 22(5): 1137-1150

Low D, Subramaniam R, Lin L, Aomatsu T, Mizoguchi A, Ng A, DeGruttola A, Lee C-G, Elias JA, Andoh A, Mino-Kenudson M, and Mizoguchi E..Chitinase 3-like 1 induces survival and proliferation of intestinal epithelial cells during chronic inflammation and colitis-associated cancer by regulating S100A9" Oncotarget 2015, 6: 36535-36550

Low D, Poltrak A, Mizoguchi A, Mino-Kenudson M, and Mizoguchi E.  High endogenous expression of Chitinase 3-like 1 and excessive epithelial proliferation with colonic tumor formation in MOLF/EiJ mice. Plos One 2015, e0139149

Nishida A  Lau CW, and Mizoguchi A:  Examination of the role of galectins in intestinal inflammation, Methods Mol Biol 2015, 1207, 231-248

溝口充志、溝口恵美子 診療に必要な炎症性腸疾患の病態の知識 日本医師会雑誌 2015, 144, 23-27

Nishida A, Lau CW, Mizoguchi E, and Mizoguchi A.  Regulatory B cells in mouse models of intestinal inflammation.  Methods Mol Biol  2014, 1190:227-241, 2014

Tran HT, Lee IA, Low D, Kamba A, Mizoguchi A, Shi HN, Lee CG, Elias JA, Mizoguchi E.  Chitinase 3-like 1 Synergistically Activates IL6-mediated STAT3 Phosphorylation in Intestinal Epithelial Cells in Murine Models of Infectious Colitis. Inflamm Bowel Dis. 201420:835-46.

米国ハーバード大学医学部でPIに昇進後の業績 (2003-2014)
Caballero-Franco C, Choo M-K, Sano Y, Ritprajak P, Sakurai H, Otsu K, Mizoguchi A, and Park JM: Tuning of protein kinase circuitry by p38 is vital for epithelial tissue homeostasis.  J Biol Chem 2013, 288:23788-23797.

Nishida A, Nagahama K, Imaeda H, Ogawa A, Lau CW, Kobayashi T, Hisamatsu T, Mizoguchi E, Ikeuchi H, Hibi T, Fukuda M, Andoh A, Blumberg RS, and Mizoguchi A. Inducible colitis-associated glycome capable of stimulating the proliferation of memory CD4+ T cells.  J Exp Med, 209:2383-2394, 2012

Nishida A, Lau CW, Zhang M, Andoh A,  Shi HN, Mizoguchi E, and Mizoguchi A. The Membrane-bound mucin Muc1 regulates Th17-cell responses and colitis in mice. Gastroenterology, 142:865-874, 2012

Nagatani K, Wang S, Llado V, Lau CW, Li Z, Mizoguchi A,  Nagler CR, Shibata Y, Reinecker HC, Mora JR, Mizoguchi E.  Chitin-microparticles for the control of intestinal inflammation.  Inflammatory Bowel Disease, 18:1698-1710, 2012

Chu C, Pekow J, Llado V, Lau CW, Mizoguchi A, Mino-Kenndson M, Bissonn M, and Mizoguchi E. Chitinase 3-like-1 (CHI3L1/YKL-40) expression in colonic epithelial cells as a potentially novel marker for colitis-associated neoplasia. Am J Pathol 179:1494-1503, 2011

Parekkadan B, Upadhyay R, Dunham J, Iwamoto Y, Mizoguchi E, Mizoguchi A, Weissleder R, and Yamush ML.  Bone marrow stromal cell transplants for the treatment of experimental enterocolitis requires host CD11b+ splenocytes.  Gastroenterology 140:966-975, 2011 

Biswas A, Liu Y, Hao L, Mizoguchi A, Salzman NH, Bevins CL, and Kobayashi KS.  Induction and rescue of NOD2-dependent Th1-driven granulomatous inflammation of the ileum.  Proc Natl Acad Sci USA 107:14739-14744, 2010

Kim P, Chung E, Yamashita H, Hung KE, Mizoguchi A, Kucherlapati R, Fukumura D, Jain RK, and Yun SH. In vivo wide-area cellular imaging by side-view endomicroscopy.  Nat Method 7:303-305., 2010 

Matharu K, Mizoguchi E, Alonso C, Nguyen D, Mingle B, Iweala OI, McBee ME, Stefka A, Prioult G, Haigis KM, Bhan AK, Snapper SB, Murakami H, Schauer DB, Reinecker HC, Mizoguchi A, Nagler CR. TLR4 mediated regulation of spontaneous Helicobacter-dependent colitis in IL-10 deficient mice.  Gastroenterolgy 137:1380-1390, 2009

Medoff  BD, Seed B, Sandall BJ, Landry A, Nagahama K, Mizoguchi A, Luster AD, and Xavier R.  Differential requirement for CARMA1 in agonist-selected T cell development.  Eur J Immunol 39:78-84, 2009

Shimomura Y, Ogawa A, Kawada M, Sugimoto K, Mizoguchi E, Shi H-N, Pillai S, Bhan AK, and Mizoguchi A. A unique B-2 B cell subset in the intestine. J Exp Med  205:1357-1368, 2008

Sugimoto K, Ogawa A, Mizoguchi E, Shimomura Y, Andoh A, Bhan AK, Blumberg RS, Xavier RJ, and Mizoguchi A.  IL-22 ameliorates intestinal inflammation in a mouse model of ulcerative colitis.       J Clin Invest 118:534-544, 2008

Nagahama K, Ogawa A, Shirane K, Shimomura Y, Sugimoto K, and Mizoguchi A.  Protein kinase C q plays a fundamental role for induction of different types of chronic colitis.  Gastroenterology 134:459-469, 2008

Shimomura Y, Mizoguchi E, Sugimoto K, Kibe R, Benno Y, Mizoguchi A, and Bhan AK.  Regulatory role of B-1 B Cells in Chronic Colitis.  Int Immunol 20:729-737, 2008

Nanno M, Kanari Y, Naito T, Inoue N, Hisamatsu T, Chinen H, Sugimoto K, Shimomura Y, Yamagishi H, Shiohara T, Suematsu M, Mizoguchi A, Hibi T, Bhan AK and Ishikawa H.  Exacerbating Role of gd T Cells in Chronic Colitis of T cell Receptor a Mutant Mice.  Gastroenterology 134:481-490, 2008

Mizoguchi E, Hachiya Y, Kawada M, Nagatani K, Ogawa A, Sugimoto K, Mizoguchi A, and Podolsky DK.  TNF receptor type I-dependent activation of innate responses to reduce intestinal damage-associated mortality.  Gastroenterology 134:470-480, 2008 

Nguyen D, Cotta-de-Almedia V, Maillard MH, Mizoguchi E, Klein C, Fuss I, Nagler C, Mizoguchi A, Bhan AK, and Snapper S.  Lymphocyte-dependent and Th2 cytokine-associated colitis in mice deficient in Wiskott-Aldrich syndrome protein.  Gastroenterology 133:1188-1197, 2007

Mizoguchi A, Ogawa A, Takedatsu H, Sugimoto K, Shimomura Y, Shirane K, Nagahama K, Nagaishi T, Mizoguchi E, Blumberg RS, and Bhan AK.  Dependence of Intestinal Granuloma Formation on Unique Myeloid Dendritic-like Cells.  J. Clin. Invest. 117:605-615, 2007

Sugimoto K, Ogawa A, Shimomura Y, Mizoguchi A, and Bhan AK.  Inducible IL-12-producing B cells regulate Th2-mediated intestinal inflammation.  Gastroenterology 133:124-136, 2007

Yoshida M, Kobayashi K, Kuo TT, Bty L, Glickman JN, Claypool SM, Kaser A, Nagaishi T, Higgins D, Mizoguchi E, Walatsuki Y, Ropenian DC, Mizoguchi A, Lencer W, Blumberg RS.  Neonatal Fc receptor for IgG regulates mucosal immune responses to luminal bacteria.  J. Clin. Invest. 116:2142-2151, 2006

Abadia-Molina AC, Mizoguchi A, Faubion WA, de Jong Y, Rietdijk ST, Comiskey M, Clark K, Bhan AK, and Terhorst C.  In vivo generation of oligoclonal colitic CD4+ T cell-lines expressing a distinct T cell receptor Vb.  Gastroenterology 128:1268-1277, 2005

Hokama A, Mizoguchi E, Sugimoto K, Shimomura Y, Tanaka Y, Yoshida M, Rietdijk ST, de Jong YP, Snapper S, Terhorst C, Blumnerg RS, and Mizoguchi A: Induced reactivity of intestinal CD4+ T cells with an epithelial cell lectin, galectin-4, contributes to exacerbation of intestinal inflammation.  Immunity 20:681-693, 2004

Yoshida M, Claypool SM, Wagner JS, Mizoguchi E, Mizoguchi A, Roopenian DC, Lencer WI, and Blumberg RS: Human neonatal Fc receptor mediayes transport of IgG into luminal secretions for delivery of antigens to mucosal dendritic cells.  Immunity 20:769-783, 2004

Beck PL, Xavier R, Wong J, Ezedi I, Mashimo H, Mizoguchi A, Mizoguchi E, Bhan AK, and Podolsky DK: Paradoxical roles of different nitric oxide synthase isoforms in colonic injury.  Am. J. Physiol. 286:G137-147, 2004

Colgan S, Pitman RS, Nagaishi T, Mizoguchi A, Mizoguchi E, Mayer LF, Shao L, Sartor RB, Subjeck JR, and Blumberg RS: Intestinal heat shock protein 110 regulates expression of CD1d on intestinal epithelial cells.  J. Clin. Invest. 112:745-754, 2003

Klein C, Nguyen D, Liu C-H, Mizoguchi A, Bhan AK, Miki H, Takenawa T, Rosen FS, Alt FA, Mulligan RC, and Snapper SB: Gene therapy for Wiskott-Aldrich syndrome: rescue of T-cell signaling and amelioration of colitis upon transplantation of retrovirally transduced hematopoietic stem cells in mice.  Blood 101:2159-2166, 2003

Swat W, Xavier R, Mizoguchi A, Mizoguchi E, Fredericks J, Fujikawa K, Bhan AK, and Alt FW: Essential role for Vav1 in activation, but not development of gamma/delta T cells.  Int. Immunol. 15:215-221, 2003
Mizoguchi E, Xavier R, Reinecker H-C, Uchino H, Bhan AK, Podolsky DK, and Mizoguchi A.  Colonic epithelial functional phenotype varies with type and phase of experimental colitis.  Gastroenterology 125:148-161, 2003 

米国ハーバード大学医学部でPIになる以前の業績 (1992-2003)
Mizoguchi A, Mizoguchi E, de Jong YP, Takedatsu H, Preffer FI, Terhorst C, and Bhan AK: Role of CD5 expression on gamma/delta T cell mediated distinct immune functions: development of germinal center and chronic intestinal inflammation. Int. Immunol. 15:97-108, 2003

Neurath MF, Weigmann B, Finotto S, Hildner K, Glickman J, Nieuwenhuis E, Iijima H, Mizoguchi A, Mizoguchi E, Autshbach F, Schurmann G, Mueller-Lobeck H, Bartsch B, Galle PR, Bhan AK, Sullivan BM, Szabo SJ, Glimcher LH, and Blumberg RS: The transcription factor T-bet regulates mucosal T cell activation in experimental colitis and Crohn’s disease. J. Exp. Med. 195:1129-1143, 2002

Mizoguchi A, Mizoguchi E, Takedatsu H, Blumberg RS, and Bhan AK:  Chronic intestinal inflammatory condition generates IL-10 producing regulatory B cell subset characterized by CD1d upregulation. Immunity 16:219-230, 2002

Mizoguchi E, Mizoguchi A, Takedatsu H, Cario E, de Jong YP, Ooi CJ, Xavier RJ, Terhorst C, Podolsky DK, and Bhan AK:  Role of tumor necrosis factor receptor 2 (TNFR2) in colonic epithelial hyperplasia and chronic intestinal inflammation. Gastroenterology 122:134-144, 2002

Mizoguchi A, Mizoguchi E, Saubermann LJ, Higaki K, Blumberg RS, and Bhan AK:  Limited CD4 T-cell diversity associated with colitis in T cell receptor alpha mutant mice requires a T helper 2 environment. Gastroenterology 119:983-995, 2000

Andres PG, Beck PL, Mizoguchi E, Mizoguchi A, Bhan AK, Dawson T, Kuziel WA, Maeda N, MacDermott RP, Podolsky DK, and Reinecker H-C:  Mice with a selective deletion of the chemokine receptors CCR5 and CCR2 are protected from DSS-mediated colitis.  Lack of CCR5 expression results in Th2 type immune response in the intestine.  J. Immunol. 164:6303-6312, 2000
Mizoguchi E, Mizoguchi A, Preffer FI, and Bhan AK:  Regulatory function of mature B cells via costimulatory pathway in a murine colitis model. Int. Immunol 12: 597-605, 2000

Morales VM, Christ A, Watt SM, Kim HS, Johnson KW, Utku N, Texieira AM, Mizoguchi A, Mizoguchi E, Russell GJ, Russell SE, Bhan AK, Freeman GJ, and Blumberg RS: Regulation of human intestinal intraepithelial lymphocyte cytolytic function by biliary glycoprotein (CD66a). J. Immunol. 163:1363-1370, 1999

Mizoguchi A, Mizoguchi E, and Bhan AK: The critical role of interleukin-4 but not interferon-gamma in the pathogenesis of colitis in T cell receptor alpha mutant mice. Gastroenterology 116:320-326, 1999

Mizoguchi E, Mizoguchi A, and Bhan AK: Role of cytokines in the early stages of chronic colitis in TCR alpha-mutant mice.  Lab. Invest. 76:385-397, 1997

Mizoguchi E, Mizoguchi A, Chiba C, Niles JL, and Bhan AK: Anti-neutrophil cytoplasmic antibodies producing B cells in TCR alpha-mutant mice with chronic colitis.  Gastroenterology 113:1828-1835, 1997

Mizoguchi A, Mizoguchi E, Smith RN, Preffer FI, and Bhan AK: Suppressive role of B cells in chronic colitis of T cell receptor alpha mutant mice.  J. Exp. Med. 186: 1749-1756, 1997

Mizoguchi A, Mizoguchi E, Chiba C, Spiekermann G, Tonegawa S, Nagler-Anderson C, and Bhan AK: Cytokine imbalance and autoantibody production in TCR-alpha mutant mice with inflammatory bowel disease.  J. Exp. Med. 183:847-856, 1996

Mizoguchi A, Mizoguchi E, Chiba C, and Bhan AK: Role of appendix in the development of inflammatory bowel disease in TCR-alpha mutant mice. J. Exp. Med. 184:707-715, 1996

Mizoguchi A, Mizoguchi E, Tonegawa S, and Bhan AK: Alteration of polyclonal to oligoclonal immune response to cecal aerobic bacterial antigens in TCR-alpha mutant mice with inflammatory bowel disease.  Int. Immunol. 8:1387-1394, 1996

Maruiwa M, Mizoguchi A, Russell GJ, Narula N, Stronska M, Mizoguchi E, Rabb H, Arnaout MA, and Bhan AK: Anti-KCA-3, a monoclonal antibody reactive with a rat complement C3 receptor, distinguishes Kupffer cells from other macrophages.  J. Immunol. 150:4019-4030, 1993

久留米大学医学部 大学院生時代の業績 (1989-1992)
Yano H, Mizoguchi A, Fukuda K, Haramaki M, Ogasawara S, Momosaki S, and Kojiro M: The herbal medicine Sho-saiko-to inhibits proliferation of cancer cell lines by inducing apoptosis and arrest at the G0/G1 phase.  Cancer. Res. 54:448-454, 1994

Yano H, Iemura A, Fukuda K, Mizoguchi A, Haramaki M, and Kojiro M: Establishment of two distinct human hepatocellular carcinoma cell lines from a single nodule showing clonal differentiation of cancer cells.  Hepatology 18:320-327, 1993           

Futagami-Mizoguchi E, Yamada A, Mizoguchi A, Imai Y, and Yokoyama MM: LFA-1 expression on exocrine glands as a potential novel marker of malignant disease.  Am. J. Pathol. 143:672-677, 1993

溝口充志小柴胡湯水可溶成分における培養ヒト肝・胆道系癌細胞株に対する増殖抑制効果の検討  和漢医薬学会誌  9:110-117, 1992

Iemura A, Yano H, Mizoguchi A, and Kojiro M: A cholangiocellular carcinoma nude mouse strain showing histologic alteration from adenocarcinoma to squamous cell carcinoma.  Cancer 70:415-422, 1992

Yano H, Maruiwa M, Iemura A, Mizoguchi A, and Kojiro M: Establishment and characterization of a new human extrahepatic bile duct carcinoma cell line (KMBC). Cancer 69:1664-1673., 1992

Nishida A, Lau CW, Mizoguchi E, and Mizoguchi A.  “Regulatory B cells in mouse models of intestinal inflammation” in Methods in Molecular Biologyedited by Dr. Vitale, Springer publisher, 2014

Low D, Mizoguchi A, and Mizoguchi E. DNA methylation in inflammatory bowel disease and beyond.  World Journal of Gastroenterology. 2013, 19:5238-5249.

Mizoguchi A and Andoh A:  “Chapter 22, Mouse models of IBD for drug discovery” in Animal Models for Human Diseases edited by Michael Conn, Elseiver Publisher, 2013, 499-527

Mizoguchi E, Mizoguchi A, and Bhan AK:  “Insights from Recent Advances in Animal Models of Inflammatory Bowel Disease” in Molecular Genetics in Inflammatory Bowel Disease, edited by D’Amato M and Rioux J, Springer Publisher, 2013

Mizoguchi A. Healing of intestinal inflammation by IL-22. Inflammatory Bowel Disease, 2012, 18:1777-1784. 
Mizoguchi A.:  “Animal models of IBD” in Animal models of molecular pathology, Book series: Progress in Molecular Biology and Translational Science, edited by Michael Conn, Elseiver Publisher, 2012, 105: 263-320  
Mizoguchi A and Bhan AK: “Immunobiology of B cells in inflammatory bowel disease” in Crohn’s Disease and Ulcerative Colitis, edited by Daniel C. Baumgart, Springer Publisher, 161-168, 2012

Stappenbeck TS, Rioux JD, Mizoguchi A, Saitoh T,Huett A, Darfeuille-Michaud A, Wileman T, Carding S, Mizushima N, Akira S, Parkes M, and Xavier RJ. Crohn disease, A current perspective on genetics, autophagy and Immunity. Autophagy2011, 7: 335-374.

溝口充志: Regulatory B細胞“Breg”による免疫抑制シグナル, 分子消化器病 8:172-177, 2011

溝口充志: Overview:IBD Immunology の“イロハ”  Intestine臨床医学出版 15:1-9, 2011

Mizoguchi A and Mizoguchi E:  Animal models of IBD: linkage to human disease.  Current Opinion in Pharmacology 2010, 10:578-587.

Mizoguchi A and Mizoguchi E: IBD: past, present and future, lesson from animal models.  Journal of Gastroenterology2008, 43:1-17.

Hokama A, Mizoguchi E, and Mizoguchi A: Roles of galectins in inflammatory bowel disease.  World J. Gastroenterol. 2008, 14:5133-5137.

Mizoguchi E, and Mizoguchi A: Is the sugar always sweet in intestinal inflammation?  Immunol Res.  2007, 37:47-60

下村泰代、杉本健、長濱清隆、溝口恵美子、溝口充志: 腸管肉芽腫形成のための新しい腸管樹状細胞 分子消化器病  4:97-103 , 2007

Mizoguchi A, and Bhan AK: A case for regulatory B cells. J. Immunol.  2006, 176:705-710.

Mizoguchi A, Mizoguchi E, and Bhan AK: Immune networks in animal models of inflammatory bowel disease.  Inflammatory Bowel Disease,2003, 9: 246-259.

Bhan AK, Mizoguchi E, Smith RN, and Mizoguchi A: Spontaneous chronic colitis in TCRalpha mutant mice an experimental model of human ulcerative colitis. Int. Rev. Immunol. 2000, 19:123-138

Bhan AK, Mizoguchi E, Smith RN, and Mizoguchi A: Colitis in transgenic and knockout animals as models of human inflammatory bowel disease.  Immunol. Rev.1999, 169:195-207

Bhan AK, Mizoguchi E., Smith RN, and Mizoguchi A: Lessons for human inflammatory bowel disease from Experimental models.  Curr. Opin. Gastroenterology  1999, 15:285-290

Bhan AK, Mizoguchi E, and Mizoguchi A: New model of chronic intestinal inflammation. Curr. Opin. Gastroenterology1994, 10:633-638.