Selected Publications from Dr. Chang H. Kim and the Immunology & Hematopoiesis Lab

Dr. Kim and the Immunology & Hematopoiesis Lab lab have published approximately 100 articles and have over 8000 total citations. For a full list of his, and the lab's, published work, visit the NIH's PubMed.

Our published work is divided into 5 different areas:

1) Identification of the roles of retinoic acid and nuclear hormones in regulation of immune responses.

We discovered the role of retinoic acid in inducing FoxP3+ regulatory T cells. We demonstrated the in vivo role of vitamin A in regulation of inflammatory bowel diseases. We also found the critical role of this hormone for the effector function of Th17 cells in the gut. We also identified the female sex hormone progesterone is highly immune regulatory and generates FoxP3+ and FoxP3- regulatory T cells.

2) Roles of the gut microbial metabolites short chain fatty acids in regulation of immune responses.

The commensal bacteria in the gut produce metabolites that are important for hosts in many different aspects. We have been studying the role of short-chain fatty acids (SCFAs) in regulation of mucosal immunity mediated by epithelial cells, lymphocytes and antigen presenting cells. We found that SCFAs condition epithelial cells to efficiently mount immune responses for clearance of invading bacteria in the gut. We also found the important role of SCFAs in promoting both effector (Th17 and Th1) and IL-10-produing regulatory T cells. SCFAs also metabolically activate immune cells for regulation of their functions.

3) Identification of CXCR5+ T-fh and Tfr cells specialized in helping or regulating B cells.

We found T cells specialized in regulating B cells in germinal centers (called T-fh cells or more specifically T-GC cells) in human lymphoid tissues. We also discovered FoxP3+ T cells that are migrating to B cell follicles and regulate B cell differentiation into plasma B cells. These findings precede other studies in mice by a decade and have sustaining impacts in the field.

4) Trafficking mechanisms of functionalized specialized lymphocytes.

We discovered key trafficking receptors and migration behavior of specialized T cell subsets such as Tregs, Th1, Th17, and NKT cells and innate lymphoid cells. We studied the trafficking of lymphocytes not only in the steady state but also in diseased conditions such as inflammation and cancer. Through the two decades of research, we established unique and shared migration programs of immune cell populations for migration and cell-cell interaction. We established that tissue-derived factors such as retinoic acid, cytokines, and metabolites are important regulators of immune cell trafficking.

5) Migration of hematopoietic stem and progenitor cells.

We found that SDF-1 (now commonly called CXCL12) regulates the migration of stem and progenitor cells and demonstrated that it is the most important trafficking factor for hematopoietic stem and progenitor cells in the bone marrow. This work started when the PI was in Dr Hal Broxmeyer’s laboratory at Indiana University School of Medicine in mid-1990’s. We demonstrated that it is the most efficacious chemoattractant for primitive T cell progenitors in the thymus. This set the stage for the widespread research on SDF-1 (also called CXCL12) in regulation of cell migration and hematopoiesis. Utilizing transgenic mice, we further found also that SDF-1 is an important growth factor for stem and progenitor cells.

  • Kim CH, Pelus LM, White JR, Appelbaum E, Johanson K, and Broxmeyer HE, CKb-11/MIP-3b/ELC is an efficacious chemoattractant for T- and B-cells. J. Immunol., 1998, 160:2418-2424.

  • Kim CH, Pelus LM, White JR, and Broxmeyer HE. Rapid communication: Differential chemotactic behavior of developing T cells in response to thymic chemokines. Blood, 1998, 91:4434-4443.

  • Kim CH, Pelus LM, White JR, and Broxmeyer HE. MIP-3b/ELC/CKb-11, a CC chemokine, is a chemoattractant for myeloid progenitor cells with a specificity for macrophage progenitors. J. Immunol., 1998, 161:2580-2585.

  • Kim CH, Qu C, Hangoc G, Cooper S, Feng G-S, and Broxmeyer HE, Abnormal chemokine induced responses of immature and mature hematopoietic cells from motheaten mice: Implication of the protein tyrosine phosphatase SHP-1 in chemokine responses, 1999, J. Exp. Med., 190:681-690.

  • Youn BS, Kim CH, Smith F, Broxmeyer HE, TECK, an efficacious chemoattractant for human thymocytes, uses GPR-9-6/CCR9 as a specific receptor. 1999, Blood. 94:2533-2536.

  • Kim CH, Hangoc G, Cooper S, Helgason CD, Yew S, Humphries RK, Krystal G, and Broxmeyer HE, Altered responsiveness to chemokines due to targeted disruption of SHIP. 1999, J. Clin. Invest. 104:1751.

  • Braun SE, Chen SE, Foster RG, Kim CH, Hromas R, Broxmeyer, HE, Cornetta K, The CC chemokine CKb-11/MIP-3b/ELC/Exodus3 mediatesnbsp tumor rejection of murine breast cancer cells through natural killer cells. 2000, J. Immunol. 164:4025.

  • Andrew DP, Ruffing N, Kim CH (co-first authors), Miao A, Heath H, You-Li, Murphy K, Butcher EC, Wu L, CCR4 expression defines a major subset of circulating non-intestinal memory T cells of both Th1 and Th2 potential. 2001, J. Immunol. 166:103.

  • Kim CH, Kunkel, EJ, Boisvert J, Johnston B, Campbell JJ, Genovese MC, Greenberg HB, and Butcher EC. Bonzo/CXCR6 defines polarized Type 1 memory/effector T cell subsets with extra-lymphoid tissue homing potential. 2001, J. Clin. Invest.107: 595.

  • Kim CH, Rott LS, Clark-Lewis I, Campbell DJ, Wu L, Butcher EC. Subspecialization of CXCR5+ T cells: B helper activity is focused in a germinal center-localized subset of CXCR5+ T cells. 2001, J. Exp. Med. 193:1373.

  • Campbell DJ, Kim CH and Butcher EC, Separable populations of effector CD4+ T cells mediate B cell help and tissue inflammation. 2001, Nature Immunology, 9:876-881.

  • Kim CH, Rott LS, Kunkel EJ, Genovese M, Andrew DP, Wu L, and Butcher EC. Rules of chemokine receptor association with T cell polarization in vivo. 2001, J. Clin. Invest, 108:1331.

  • Kim CH, Johnston Brent and Butcher EC, Trafficking machinery of NKT cells: differential chemokine receptor expression among NKT cell subsets with distinct cytokine-producing capacity. 2002, Blood. 2002;100:11-16.

  • Roy M, Kim CH, Butcher EC. Cytokine regulation of B cell homing machinery. 2002, J. Immunol. 169:1676.

  • Broxmeyer HE, Cooper S, Kohli L, Hangoc G, Lee Y, Mantel C, Clapp DW, Kim CH. Transgenic Expression of Stromal Cell-Derived Factor-1/CXC Chemokine Ligand 12 Enhances Myeloid Progenitor Cell Survival/Antiapoptosis In Vitro in Response to Growth Factor Withdrawal and Enhances Myelopoiesis In Vivo. J. Immunol. 2003, 170:421-429.

  • Kunkel EJ, Kim CH, Lazarus NH, Vierra MA, Soler D, Bowman EP, Butcher EC. CCR10 expression is a common feature of circulating and mucosal epithelial tissue IgA Ab-secreting cells. J Clin Invest. 2003, 111:1001-10.

  • Johnston B, Kim CH, Soler D, Emoto M, Butcher EC. Differential chemokine responses and homing patterns of murine TCRalphabeta NKT cell subsets. J Immunol. 2003, 171:2960-9.

  • Kim CH, Nagata K, and Butcher EC. Dendritic Cells Support Sequential Reprogramming of Chemoattractant Receptor Profiles During Naive to Effector T Cell Differentiation. J. Immunol. 2003. 171(1):152-8.

  • Kim CH, Lim HW, Kim JR, Rott L, Hillsamer P, Butcher EC. Unique gene expression program of human germinal center T cells. 2004. Blood. 104: 1952-1960.

  • Lim HW, Hillsamer P, Kim CH. Regulatory T cells acquire migratory capacity to follicles upon T cell activation and suppress GC-T helper cell-driven B cell responses. 2004, J. Clin. Invest. 114:1640-1649.

  • Kim JR, Lim HW, Hillsamer P, Kim CH. Human CD57+ germinal center-T cells are the major helpers for GC-B cells and induce class switch recombination. BMC Immunology 2005, 6:3.

  • Lim, HW, Hillsamer P, Banham AH, and Kim CH, Cutting Edge: Direct Suppression of B Cells by CD4+CD25+ Regulatory T Cells , J Immunol 2005 175: 4180-4183.

  • Broxmeyer HE, Cooper S, Hangoc G, Kim CH. Stromal cell-derived factor-1/CXCL12 selectively counteracts inhibitory effects of myelosuppressive chemokines on hematopoietic progenitor cell proliferation in vitro. 2005. Stem Cells Dev. 14: 199-203.

  • Lim HW, Broxmeyer HE, Kim CH. Regulation of trafficking receptor expression in human forkhead box p3+ regulatory T cells. J Immunol. 2006 177(2):840-51.

  • Lee JH, Kang SG, Kim CH. FoxP3+ T cells undergo conventional first switch to lymphoid tissue homing receptors in thymus but accelerated second switch to non-lymphoid tissue homing receptors in secondary lymphoid tissues. 2007, J Immunol 2007 178: 301-311.

  • Kang SG, Piniecki RJ, Hogenesch H, Lim HW, Wiebke E, Braun SE, Matsumoto S, Kim CH.  Identification of a chemokine network that recruits FoxP3(+) regulatory T cells into chronically inflamed intestine. Gastroenterology. 2007, 3: 966-81.

  • Lim HW, Kim CH. Loss of IL-7 Receptor alpha on CD4+ T Cells Defines Terminally Differentiated B Cell-Helping Effector T Cells in a B Cell-Rich Lymphoid Tissue. J Immunol. 2007, 179:7448-56.

  • Kang SG, Lim HW, Andrisani OM, Broxmeyer HE, Kim CH. Vitamin A metabolites induce gut-homing FoxP3+ regulatory T cells. J Immunol. 2007, 179(6):3724-33.

  • Lim HW, Lee J, Hillsamer P, Kim CH. Human Th17 cells share major trafficking receptors with both polarized effector T cells and FOXP3+ regulatory T cells.
    J Immunol. 2008 Jan 1;180(1):122-9.

  • Wang C, Kang SG, Lee J, Sun Z, Kim CH. The roles of CCR6 in migration of Th17 cells and regulation of effector T-cell balance in the gut. Mucosal Immunol. 2009 Mar;2(2):173-83   

  • Kang SG, Wang C, Matsumoto S, Kim CH. High and low vitamin A therapies induce distinct FoxP3+ T cell subsets and effectively control intestinal inflammation. Gastroenterology. 2009 Oct;137(4):1391-402.

  • Lee JH, Wang C, Kim CH. FoxP3+ regulatory T cells restrain splenic extramedullary myelopoiesis via suppression of hemopoietic cytokine-producing T cells. J Immunol. 2009 Nov 15;183(10):6377-86.
  • Betz BC, Jordan-Williams KL, Wang C, Kang SG, Liao J, Logan MR, Kim CH, Taparowsky EJ. Batf coordinates multiple aspects of B and T cell function required for normal antibody responses. J Exp Med. 2010 Apr 26.
  • Wang C, Kang SG, Hogenesch H, Love PE, Kim CH. Retinoic Acid Determines the Precise Tissue Tropism of Inflammatory Th17 Cells in the Intestine. J Immunol. 2010, 184, 5519 -5526 
  • Kang SG, Park J, Cho JY, Ulrich B, Kim CH. Complementary roles of retinoic acid and TGF-beta1 in coordinated expression of mucosal integrins by T cells. Mucosal Immunol. 2011, PMID: 20664575
  • Lee JH, Ulrich B, Cho J, Park J, Kim CH. Progesterone promotes differentiation of human cord blood fetal T cells into T regulatory cells but suppresses their differentiation into Th17 cells. J Immunol. 2011 Aug 15;187(4):1778-87. PMID: 21768398
  • Wang C, Lee JH, Kim CH. Optimal population of FoxP3+ T cells in tumors requires an antigen priming-dependent trafficking receptor switch. 2012. PLoS One. 2012;7(1):e30
  • Lee JH, Lydon JP, Kim CH. Generation of induced regulatory T cells with improved stability and suppressive activity with progesterone. Eur. J. Immunol. 2012 Jun 28. doi: 10.1002/eji.201142317
  • Chang J, Thangamani S, Kim MH, Ulrich B, Morris SM Jr, Kim CH. Retinoic acid promotes the development of Arg1-expressing dendritic cells for the regulation of T-cell differentiation. Eur J Immunol. 2013 Apr;43(4):967-78. doi: 10.1002/eji.201242772.
  • Wang C, Thangamani S, Kim M, Gu BH, Lee JH, Taparowsky EJ, Kim CH. BATF is required for normal expression of gut-homing receptors by T helper cells in response to retinoic acid. J Exp Med. 2013 Mar 11;210(3):475-89. doi: 10.1084/jem.20121088.
  • Kim MH, Kang SG, Park JH, Yanagisawa M, Kim CH. Short-Chain Fatty Acids Activate GPR41 and GPR43 on Intestinal Epithelial Cells to Promote Inflammatory Responses in Mice. Gastroenterology. 2013 May 7. doi:pii: S0016-5085(13)00708-7. 10.1053/j.gastro.2013.04.056.
  • Jabeen R, Goswami R, Awe O, Kulkarni A, Nguyen ET, Attenasio A, Walsh D, Olson MR, Kim MH, Tepper RS, Sun J, Kim CH, Taparowsky EJ, Zhou B, Kaplan MH.  Th9 cell development requires a BATF-regulated transcriptional network. J Clin Invest. 2013 Oct 8. pii: 69489. doi: 10.1172/JCI69489. 
  • Park J, Kim M, Kang SG, Jannasch AH, Cooper B, Patterson J, Kim CH. Short-chain fatty acids induce both effector and regulatory T cells by suppression of histone deacetylases and regulation of the mTOR-S6K pathway. Mucosal Immunol. 2014 Jun 11. doi: 10.1038/mi.2014.44
  • Kim CH, Hashimoto-Hill S, Kang SG. Human Tfh and Tfr cells: identification and assessment of their migration potential. Methods Mol Biol. 2015;1291:175-86. doi: 10.1007/978-1-4939-2498-1_15.
  • Thangamani S, Kim M, Son Y, Huang X, Kim H, Lee JH, Cho J, Ulrich B, Broxmeyer HE, Kim CH.Cutting edge: progesterone directly upregulates vitamin d receptor gene expression for efficient regulation of T cells by calcitriol.
    J Immunol. 2015 Feb 1;194(3):883-6. doi: 10.4049/jimmunol.1401923. Epub 2014 Dec 29.
  • Kim MH, Taparowsky EJ, Kim CH. Retinoic Acid Differentially Regulates the Migration of Innate Lymphoid Cell Subsets to the Gut. Immunity. 2015; 43(1):107-19. NIHMSID: NIHMS698201

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